Controlled growth of microorganisms

ABSTRACT

It can be useful to regulate the growth of microbial cells. Some embodiments herein provide genetically engineered microbial cells that can produce bacteriocins to control the growth of microbial cells. In some embodiments, microbial cells are contained within a desired environment. In some embodiments, contaminating microbial cells are neutralized. In some embodiments, a first microbial cell type regulates the growth of a second microbial cell type so as to maintain a desired ratio of the two cell types.

RELATED APPLICATIONS

The present application claims the benefit of U.S. ProvisionalApplication Ser. No. 61/867,510, filed on Aug. 19, 2013, which is herebyincorporated by reference in its entirety.

REFERENCE TO SEQUENCE LISTING

The present application is being filed along with a Sequence Listing inelectronic format. The Sequence Listing is provided as a file entitledSEQUENCESYNG001A.TXT, created and last saved on Aug. 11, 2014, which is380,081 bytes in size, and updated by a file entitledSEQUENCESYNG001AREPLACEMENT.TXT, created and last saved on Aug. 27,2014, which is 380,201 bytes in size. The information in the originalelectronic format of the Sequence Listing and updated electronic formatof the Sequence Listing is incorporated herein by reference in itsentirety.

BACKGROUND

Humans have used microbial organisms to generate products since thebeginning of human history, for example in processing foods such ascheese, beer, and wine. During the centuries, microbialorganism-mediated processes have been studied and scaled-up, often bycontrolling fermentation conditions or identification of phenotypiccharacteristics of microbial organisms.

Presently, many products are produced using a process that involvesmicrobial organisms. In laboratories, and in some pharmaceuticalmanufacturing processes, microbial organisms, including geneticallyengineered microbial organisms, can be cultured in sterile, controlledenvironments. On the other hand, feedstocks used for various industrialprocesses involving microorganisms are not sterile, and may contain avariety of strains and species of microorganisms. As such, geneticallyengineered microorganisms for laboratory and pharmaceutical processesare not necessarily suited for processes, such as industrial processes,which involve using feedstocks or which are exposed to othermicroorganisms in the environment which could potentially contaminatethe culture and which may also involve, changing environmentalconditions. Herein microorganisms which have been engineered to controltheir own growth and the growth of other microorganisms and/or torespond to changes in their environment are described. Suchmicroorganisms are suitable for growth in non-sterile, less rigidlycontrolled feedstocks. Such microorganisms can be useful for robust,consistent production of a desired product across a range of differentfeedstocks and environments.

FIELD

Embodiments herein relate generally to the control of growth ofmicroorganisms. More particularly, some embodiments herein relate tomicroorganisms engineered for regulated growth in response to othermicroorganisms and/or conditions of the culture environment, and methodsof making and using such engineered microorganisms.

SUMMARY

One embodiment disclosed herein includes a first microbial cellcomprising a nucleic acid encoding a secreted bacteriocin which controlsthe growth of a second microbial cell and a nucleic acid which confersresistance to the secreted bacteriocin is provided, in which the firstmicrobial cell has been genetically engineered to allow the expressionor activity of the nucleic acid which confers resistance to thebacteriocin to be regulated. According to some aspects of thisembodiment, the expression or activity of the nucleic acid which confersresistance to the bacteriocin is reduced to a level which causes thefirst microbial cell to be neutralized by the bacteriocin if the firstmicrobial cell is released from a desired growth environment. Accordingto some aspects of this embodiment, the first microbial cell has beengenetically engineered to make a desired product. According to someaspects of this embodiment, the secreted bacteriocin further has beenselected to maintain at least one condition within a culture in whichthe first microbial cell is producing the desired product. According tosome aspects of this embodiment, the culture comprises at least oneinvading microbial organism. According to some aspects of thisembodiment, the at least one condition of the culture comprisescontrolling the growth of the second microbial cell, wherein the secondmicrobial cell is a common contaminate of the culture. According to someaspects of this embodiment, the second microbial cell is a differentstrain, species or genus than the first microbial cell. According tosome aspects of this embodiment, the microbial cell further comprises anucleic acid encoding a second secreted bacteriocin which controls thegrowth of a third microbial cell and a nucleic acid which confersresistance to the secreted second bacteriocin, and also the firstmicrobial cell has been genetically engineered to allow the expressionor activity of the nucleic acid which confers resistance to thebacteriocin to be regulated. According to some aspects of thisembodiment, the bacteriocin kills the second microbial cell. Accordingto some aspects of this embodiment, the bacteriocin reduces the growthrate of the second microbial cell. According to some aspects of thisembodiment, the bacteriocin arrests the growth of the second microbialcell. According to some aspects of this embodiment, the transcription ofthe nucleic acid conferring resistance to the bacteriocin is under thecontrol of a regulatable promoter. According to some aspects of thisembodiment, the activity of a polypeptide encoded by the nucleic acidconferring resistance to the bacteriocin is regulatable. According tosome aspects of this embodiment, the nucleic acid encoding thebacteriocin is on a chromosome of the microbial cell. According to someaspects of this embodiment, the nucleic acid conferring resistance tothe bacteriocin is on a plasmid. According to some aspects of thisembodiment, the nucleic acid encoding the bacteriocin is on a chromosomeof the microbial cell, and the nucleic acid conferring resistance to thebacteriocin is on a plasmid. According to some aspects of thisembodiment, the nucleic acid encoding the bacteriocin and the nucleicacid conferring resistance to the bacteriocin are on one or moreplasmids. According to some aspects of this embodiment, the firstmicrobial cell is selected from the group consisting of bacteria, yeast,and algae, for example photosynthetic microalgae.

Another embodiment disclosed herein includes a method of controlling thegrowth of a second microbial cell in a culture medium, in which themethod includes comprising culturing a first microbial cell as describedherein in a culture medium comprising the second microbial cell underconditions in which the first microbial cell produces a bacteriocin at alevel sufficient to control the growth of the second microbial cell.According to some aspects of this embodiment, the culture is maintainedcontinually for at least 30 days, for example at least 30, 35, 40, 45,50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 110, 120, 130, 140, 150,160, 170, 180, 190, 200, 250, 300, 350, 400, 450, or 500 days. Accordingto some aspects of this embodiment, the method further includesdetecting at least one change in the culture medium, the changecomprising a presence or increase in the levels or activity of a thirdmicrobial cell, and reengineering the first microbial cell in responseto the change to produce a second bacteriocin at a level sufficient tocontrol the growth of the third microbial cell.

Another embodiment disclosed herein includes a method of detecting apresence, absence, or amount of a molecule in a culture is provided. Themethod can comprise culturing a first genetically engineered microbialcell comprising a bacteriocin under the control of a geneticallyregulatable promoter, such that the regulatable promoter is regulated bythe molecule so that either (a) the regulatable promoter drivestranscription in the presence of the molecule, but not in the absence ofthe molecule; or (b) the regulatable promoter drives transcription inthe absence of the molecule, but not in the presence of the molecule.The method can comprise isolating an amount of genomic nucleic acid ofthe first microbial cell from the culture. The method can comprisedetecting from the amount of genomic nucleic acid, a presence, absence,or quantity of a nucleic acid sequence characteristic of the firstmicrobial cell. According to some aspects of this embodiment, the methodfurther includes comparing the quantity of the nucleic acid sequencecharacteristic of the first microbial cell to a quantity of a referencenucleic acid sequence.

Another embodiment disclosed herein includes a genetically engineeredvector comprising a nucleic acid conferring resistance to a bacteriocin,in which the expression or activity of the nucleic acid is configured tochange in response to the presence, level or absence of a component of afeedstock. According to some aspects of this embodiment, the vectorfurther comprises a nucleic acid encoding the bacteriocin. According tosome aspects of this embodiment, the vector further comprises a nucleicacid which encodes a desired product.

Another embodiment disclosed herein includes a kit, which can includes aplurality of strains of a genetically engineered microbial organism, inwhich each strain has been genetically engineered to allow theexpression or activity of a nucleic acid which confers resistance to adifferent bacteriocin to be regulated.

Another embodiment disclosed herein includes a method of identifying atleast one bacteriocin which modulates the growth of at least onemicrobial cell in an industrial culture medium, in which the methodincludes contacting the industrial culture medium with a medium orcomposition comprising the at least one bacteriocin; and determiningwhether the at least one bacteriocin has a desired effect on the growthof the at least one microbial cell. According to some aspects of thisembodiment, the method includes contacting the industrial culture mediumwith at least one bacteriocin produced by a first microbial cell asdescribed herein. According to some aspects of this embodiment, the atleast one bacteriocin produced by the first microbial cell is in asupernatant obtained from a culture comprising the first microbial cell.According to some aspects of this embodiment, the method furtherincludes constructing a genetically engineered microbial cell to produceat least one bacteriocin which has been determined to have a desiredeffect on the growth of the at least one microbial cell. According tosome aspects of this embodiment, the at least one microbial cell is anorganism which is a common invader of the industrial culture medium.According to some aspects of this embodiment, the at least one microbialcell is an organism which has newly invaded an existing industrialculture.

Another embodiment disclosed herein includes a system for neutralizingundesired microbial organisms in a culture medium. The system cancomprise a first environment comprising a culture medium, and a secondenvironment comprising a second microbial organism that secretes two ormore different bacteriocins, in which the second microbial organismcomprises immunity modulators for each of the two or more differentbacteriocins, in which the second environment is in fluid communicationwith the first environment, in which the second environment isphysically separated from the first environment so that the secondmicrobial organism cannot move from the second environment to the firstenvironment, and in which the secreted two or more differentbacteriocins enter the culture medium of the first environment.According to some aspects of this embodiment, the system furthercomprises a first microbial organism in the culture medium, in which thefirst microbial organism does not secrete the two or more differentbacteriocins, and in which the first microbial organism is notneutralized by any of the two or more different bacteriocins. Accordingto some aspects of this embodiment, the first microbial organism isnon-GMO. According to some aspects of this embodiment, the firstmicrobial organism ferments a component of the culture medium. Accordingto some aspects of this embodiment, the first microbial organismdecontaminates the culture medium. According to some aspects of thisembodiment, the first microbial organism conducts photosynthesis, andthe photosynthesis comprises a substrate comprised by the culturemedium. According to some aspects of this embodiment, the secondenvironment is separated from the first environment by at least one of amembrane, a mesh, a filter, or a valve that is permeable to the two ormore different bacteriocins, but is not permeable to the secondmicrobial organisms. According to some aspects of this embodiment, thesecond microbial organism secretes at least 3 bacteriocins, for exampleat least 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or20 bacteriocins. According to some aspects of this embodiment, thesecond environment comprises at least a third microbial organism that isdifferent from the second microbial organism, and also secretesbacteriocins. According to some aspects of this embodiment, the thirdmicrobial organism secretes at least 2 bacteriocins, for example atleast 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or20 bacteriocins. Another embodiment disclosed herein includes a methodof storing a feedstock. The method can comprise providing a feedstock,providing a first microbial organism, in which the first microbialorganism secretes two or more different bacteriocins, contacting thefeedstock with the bacteriocins, and storing the feedstock for a desiredperiod of time. According to some aspects of this embodiment, contactingthe feedstock with the bacteriocins comprises contacting the feedstockwith the microbial organism. According to some aspects of thisembodiment, contacting the feedstock with the bacteriocins comprisesplacing the microbial organism in fluid communication with thefeedstock, while maintaining physical separation between the microbialorganism and the feedstock, so that the bacteriocins contact thefeedstock, but the microbial organism does not directly contact thefeedstock. According to some aspects of this embodiment, the separationis maintained by at least one or more of a membrane, a mesh, a filter,or a valve that is permeable to the two or more different bacteriocins,but is not permeable to the first microbial organism. According to someaspects of this embodiment, the method further comprises fermenting thefeedstock with a second microbial organism prior to or concurrently withcontacting the feedstock with the bacteriocins. According to someaspects of this embodiment, the fermentation comprises at least one ofproducing a desired component in the feedstock or removing an undesiredcomponent from the feedstock. According to some aspects of thisembodiment, the desired period of time comprises at least one month, forexample at least one, two, three, four, five, six, seven, eight, nine,ten, eleven, or twelve months. According to some aspects of thisembodiment, the desired period of time comprises at least six months,for example six, seven, eight nine, ten, eleven, or twelve months.According to some aspects of this embodiment, the first microbialorganism secretes at least 3 bacteriocins, for example at least 3, 4, 5,6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or bacteriocins.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a flow diagram depicting options for configuring a microbialcell to control the growth of a second microbial cell according to someof the embodiments herein.

FIG. 2A is a schematic diagram illustrating a first microbial cellcontrolling the growth of other microbial cells according to some of theembodiments herein. FIG. 2B is a schematic diagram illustrating controlof the growth of a first microbial cell when the first microbial cell isno longer in a desired growth environment according to some of theembodiments herein.

FIG. 3 is a schematic diagram illustrating a first microbial cellcontrolling growth of a second microbial cell and neutralizing aninvading cell in a desired environment according to some of theembodiments herein.

FIG. 4 is a schematic diagram illustrating a first microbial cellneutralizing a first invading cell with a first bacteriocin and secondinvading cells with a second bacteriocin in a desired environmentaccording to some of the embodiments herein.

FIG. 5 is a flow diagram illustrating methods of controlling the growthof at least a second microbial cell in culture according to someembodiments herein.

FIG. 6 is a schematic diagram illustrating a system comprising a geneticguard in accordance with some embodiments herein.

FIG. 7 is a schematic diagram illustrating a genetic guard system thatcan be useful for photosynthetic production in accordance with someembodiments herein.

FIG. 8 is a flow diagram illustrating methods of producing and usingbacteriocins in accordance with some embodiments herein.

DETAILED DESCRIPTION

According to some of the embodiments herein, genetically engineeredmicrobial organisms are provided. In some embodiments, the microbialorganisms are engineered to control the growth of the microbialpopulation in an environment such as those employing a feedstock. Asused herein, “neutralizing” activity (and variations of the same rootword) of bacteriocins can refer to either arrest of microbialreproduction, or cytotoxicity. Microbial organisms can be engineered toproduce bacteriocins, which are secreted polypeptides that canneutralize microorganisms. However, microbial organisms that producebacteriocin immunity modulators can resist certain bacteriocins. Thus,in some embodiments, a first microbial organism is engineered to secretebacteriocins. In some embodiments, the particular bacteriocins areselected based on the type of microbial cell, the types of microbialcells being regulated, the composition of the culture medium, orgeographic location (for example, to target particular contaminatingmicrobial organisms associated with a particular type of culture mediumand/or geographical location). Other microbial organisms that possessdesired characteristics for a particular environment can producebacteriocin immunity modulators (and thus survive in the presence ofbacteriocins), while undesired other microbial organisms (for examplecontaminants, microbial organisms that have lost a desiredcharacteristic or organisms which are involved in an industrial processbut whose growth or production of a particular product is not desiredunder the prevailing conditions) fail to produce bacteriocin immunitymodulators, and are thus neutralized by the bacteriocins.

Microbial Organisms

According to some aspects, genetically engineered microorganisms areprovided. As used herein, genetically engineered “microbial organism,”“microorganism,” and variations of these root terms (such aspluralizations and the like), encompasses genetic modification of anynaturally-occurring species or fully synthetic prokaryotic or eukaryoticunicellular organism, as well as Archae species. Thus, this expressioncan refer to cells of bacterial species, fungal species, and algae.

Exemplary microorganisms that can be used in accordance with embodimentsherein include, but are not limited to, bacteria, yeast, and algae, forexample photosynthetic microalgae. Furthermore, fully syntheticmicroorganism genomes can be synthesized and transplanted into singlemicrobial cells, to produce synthetic microorganisms capable ofcontinuous self-replication (see Gibson et al. (2010), “Creation of aBacterial Cell Controlled by a Chemically Synthesized Genome,” Science329: 52-56, hereby incorporated by reference in its entirety). As such,in some embodiments, the microorganism is fully synthetic. A desiredcombination of genetic elements, including elements that regulate geneexpression, and elements encoding gene products (for examplebacteriocins, immunity modulators, poison, antidote, and industriallyuseful molecules) can be assembled on a desired chassis into a partiallyor fully synthetic microorganism. Description of genetically engineeredmicrobial organisms for industrial applications can also be found inWright, et al. (2013) “Building-in biosafety for synthetic biology”Microbiology 159: 1221-1235.

A variety of bacterial species and strains can be used in accordancewith embodiments herein, and genetically modified variants, or syntheticbacteria based on a “chassis” of a known species can be provided.Exemplary bacteria with industrially applicable characteristics, whichcan be used in accordance with embodiments herein include, but are notlimited to, Bacillus species (for example Bacillus coagulans, Bacillussubtilis, and Bacillus licheniformis), Paenibacillus species,Streptomyces species, Micrococcus species, Corynebacterium species,Acetobacter species, Cyanobacteria species, Salmonella species,Rhodococcus species, Pseudomonas species, Lactobacillus species,Enterococcus species, Alcaligenes species, Klebsiella species,Paenibacillus species, Arthrobacter species, Corynebacterium species,Brevibacterium species, Thermus aquaticus, Pseudomonas stutzeri,Clostridium thermocellus, and Escherichia coli.

A variety of yeast species and strains can be used in accordance withembodiments herein, and genetically modified variants, or syntheticyeast based on a “chassis” of a known species can be provided. Exemplaryyeast with industrially applicable characteristics, which can be used inaccordance with embodiments herein include, but are not limited toSaccharomyces species (for example, Saccharomyces cerevisiae,Saccharomyces bayanus, Saccharomyces boulardii), Candida species (forexample, Candida utilis, Candida krusei), Schizosaccharomyces species(for example Schizosaccharomyces pombe, Schizosaccharomyces japonicas),Pichia or Hansenula species (for example, Pichia pastoris or Hansenulapolymorpha) species, and Brettanomyces species (for example,Brettanomyces claussenii).

A variety of algae species and strains can be used in accordance withembodiments herein, and genetically modified variants, or syntheticalgae based on a “chassis” of a known species can be created. In someembodiments, the algae comprises photosynthetic microalgae. Exemplaryalgae species that can be useful for biofuels, and can be used inaccordance with embodiments herein, include Botryococcus braunii,Chlorella species, Dunaliella tertiolecta, Gracilaria species,Pleurochrysis carterae, and Sargassum species. Additionally, many algaescan be useful for food products, fertilizer products, wasteneutralization, environmental remediation, and carbohydratemanufacturing (for example, biofuels).

Bacteriocins

As used herein, “bacteriocin,” and variations of this root term, refersto a polypeptide that is secreted by a host cell and can neutralize atleast one cell other than the individual host cell in which thepolypeptide is made, including cells clonally related to the host celland other microbial cells. As used herein, “bacteriocin” alsoencompasses a cell-free or chemically synthesized version of such apolypeptide. A cell that expresses a particular “immunity modulator”(discussed in more detail herein) is immune to the neutralizing effectsof a particular bacteriocin or group of bacteriocins. As such,bacteriocins can neutralize a cell producing the bacteriocin and/orother microbial cells, so long as these cells do not produce anappropriate immunity modulator. As such, a host cell can exert cytotoxicor growth-inhibiting effects on a plurality of other microbial organismsby secreting bacteriocins. In some embodiments, a bacteriocin isproduced by the translational machinery (e.g. a ribosome, etc.) of amicrobial cell. In some embodiments, a bacteriocin is chemicallysynthesized. Some bacteriocins can be derived from a polypeptideprecursor. The polypeptide precursor can undergo cleavage (for exampleprocessing by a protease) to yield the polypeptide of the bacteriocinitself. As such, in some embodiments, a bacteriocin is produced from aprecursor polypeptide. In some embodiments, a bacteriocin comprises apolypeptide that has undergone post-translational modifications, forexample cleavage, or the addition of one or more functional groups.

“Antibiotic,” and variations of this root term, refers to a metabolite,or an intermediate of a metabolic pathway which can kill or arrest thegrowth of at least one microbial cell. Some antibiotics can be producedby microbial cells, for example bacteria. Some antibiotics can besynthesized chemically. It is understood that bacteriocins are distinctfrom antibiotics, at least in that bacteriocins refer to gene products(which, in some embodiments, undergo additional post-translationalprocessing) or synthetic analogs of the same, while antibiotics refer tointermediates or products of metabolic pathways or synthetic analogs ofthe same.

Neutralizing activity of bacteriocins can include arrest of microbialreproduction, or cytotoxicity. Some bacteriocins have cytotoxic activity(e.g. “bacteriocide” effects), and thus can kill microbial organisms,for example bacteria, yeast, algae, synthetic micoorganisms, and thelike. Some bacteriocins can inhibit the reproduction of microbialorganisms (e.g. “bacteriostatic” effects), for example bacteria, yeast,algae, synthetic micoorganisms, and the like, for example by arrestingthe cell cycle.

It is noted that non-bacteriocin approaches have been proposed to targetvarious microbial organisms. For example, KAMORAN™ chemical has beenproposed to target Lactic Acid Bacteria (LAB) family bacteria (see UnionNationale des Groupements de Distillateurs D'Alcool, (2005) “Kamoran”).It is noted that phage has also been proposed to target LAB familybacteria (see U.S. Pub. No. 2010/0330041). It is noted that pesticideshave been proposed to target various contaminating microbial organsims(see McBride et al., “Contamination Management in Low Cost Open AlgaePonds for Biofuels Production” Industrial Biotechnology 10: 221-227(2014)). However, bacteriocins can provide numerous advantages overchemicals, pesticides, or phages. For example, bacteriocins can avoidpotentially toxic runoff or byproduct in a feedstock. For example,bacteriocins can have higher efficacy against particular undesiredmicrobial organisms than phages, chemicals, or pesticides. For example,bacteriocins can be produced by microbial organisms that undergologarithmic growth, and thus can readily be scaled-up or scaled down,whereas the scalability of phages or chemical/pesticide systems can bemore limited. For example, bacteriocins can allow for precise controlover which organisms are neutralized and which are not, for example toavoid neutralization of industrially useful microbial organisms in theculture medium. For example, phages can be difficult to produce at anindustrial scale, and also can be difficult to control, in that phagescan be infectious, can raise questions of gene control, and in thatconservation of phages can be difficult. On the other hand, bacteriocinsin accordance with some embodiments herein can comprise part of anindustrial process and thus can be involved in gene containment and/orcontrol a fermentation process via bacteriostatic activity.Additionally, the susceptibility of the microbial organisms involved inthe industrial process can be tuned via immunity control. Additionally,bacteriocins typically have a low level of toxicity for industrialapplications such as human or animal food, and it is contemplated thatbacteriocins in accordance with some embodiments herein are suitable foruse as a food preservative, such as an additive.

In some embodiments, a particular neutralizing activity (e.g. cytoxicityor arrest of microbial reproduction) is selected based on the type ofmicrobial regulation that is desired. As such in some embodiments,microbial cells are engineered to express particular bacteriocins orcombination of bacteriocins. For example, in some embodiments, microbialcells are engineered to express particular bacteriocins based on thecells being regulated. In some embodiments, for example if contaminatingcells are to be killed at least one cytotoxic bacteriocin is provided.In some embodiments, a bacteriocin or combination of bacteriocins whichis effective against contaminants which commonly occur in a particularculture, or a particular geographic location, or a particular type ofculture grown in a particular geographic location are selected. In someembodiments, for example embodiments in which reversible regulation ofmicrobial cell ratios is desired, a bacteriocin that inhibits microbialreproduction is provided. Without being limited by any particulartheory, many bacteriocins can have neutralizing activity againstmicrobial organisms that typically occupy the same ecological niche asthe species that produces the bacteriocin. As such, in some embodiments,when a particular spectrum of bacteriocin activity is desired, abacteriocin is selected from a host species that occupies the same (orsimilar) ecological niche as the microbial organism or organismstargeted by the bacteriocin.

In some embodiments, one or more bacteriocin activities are selected inadvance of culture growth, and one or more microbial organisms areengineered to generate a desired culture environment. In someembodiments, bacteriocins may be selected based on their ability toneutralize one or more invading organisms which are likely to attempt togrow in a particular culture. In another embodiment, in an industrialenvironment in which strain A makes intermediate A, and strain Bconverts intermediate A into intermediate B, strains A and B can beengineered so that an abundance of intermediate A shifts the equilibriumto favor strain B by generating a bacteriocin activity profile such thatgrowth of strain A is inhibited or prevented under these conditions,while a lack of intermediate A shifts the equilibrium to favor strain Aby generating a bacteriocin activity profile such that growth of strainB is inhibited or prevented. In some embodiments, one or morebacteriocin activities are selected based on one or more conditions ofan existing culture environment. For example, if particular invaders areidentified in a culture environment, “neutralizer” microrganisms can beengineered to produce bacteriocins to neutralize the identifiedinvaders. In some embodiments, genetically engineered cells that producebacteriocins are added to an existing culture to re-equilibrate theculture, for example if a growth of a particular microbial cell type inthe microbial cell culture is too high. In some embodiments, geneticallyengineered cells that produce bacteriocins are added to an existingculture to neutralize all or substantially all of the microbial cells ina culture, for example to eliminate an industrial culture in a cultureenvironment so that a new industrial culture can be introduced to theculture environment.

For example, in some embodiments, an anti-fungal activity (such asanti-yeast activity) is desired. A number of bacteriocins withanti-fungal activity have been identified. For example, bacteriocinsfrom Bacillus have been shown to have neutralizing activity againstyeast strains (see Adetunji and Olaoye (2013) Malaysian Journal ofMicrobiology 9: 130-13, hereby incorporated by reference in itsentirety), an Enterococcus faecalis peptide (WLPPAGLLGRCGRWFRPWLLWLQSGAQY KWLGNLFGLGPK, SEQ ID NO: 1) has been shown to have neutralizingactivity against Candida species (see Shekh and Roy (2012) BMCMicrobiology 12: 132, hereby incorporated by reference in its entirety),and bacteriocins from Pseudomonas have been shown to have neutralizingactivity against fungi such as Curvularia lunata, Fusarium species,Helminthosporium species, and Biopolaris species (Shalani and Srivastava(2008) The Internet Journal of Microbiology. Volume 5 Number 2. DOI:10.5580/27dd—accessible on the worldwide web atarchive.ispub.com/journal/the-internet-journal-of-microbiology/volume-5-number-2/screening-for-antifungal-activity-of-pseudomonas-fluorescens-against-phytopathogenic-fungi.html#sthash.d0Ys03UO.1DKuT1US.dpuf,hereby incorporated by reference in its entirety). By way of example,botrycidin AJ1316 (see Zuber, P et al. (1993) Peptide Antibiotics. InBacillus subtilis and Other Gram-Positive Bacteria: Biochemistry,Physiology, and Molecular Genetics ed Sonenshein et al., pp. 897-916,American Society for Microbiology, hereby incorporated by reference inits entirety) and alirin B1 (see Shenin et al. (1995) Antibiot Khimioter50: 3-7, hereby incorporated by reference in its entirity) from B.subtilis have been shown to have antifungal activities. As such, in someembodiments, for example embodiments in which neutralization of a fungalmicrobial organism is desired, a bacteriocin comprises at least one ofbotrycidin AJ1316 or alirin B1.

For example, in some embodiments, bacteriocin activity in a culture ofcyanobacteria is desirable. In some embodiments, bacteriocins areprovided to neutralize cyanobacteria. In some embodiments, bacteriocinsare provided to neutralize invading microbial organisms typically foundin a cyanobacteria culture environment. Clusters of conservedbacteriocin polypeptides have been identified in a wide variety ofcyanobacteria species. For example, at least 145 putative bacteriocingene clusters have been identified in at least 43 cyanobacteria species,as reported in Wang et al. (2011), Genome Mining Demonstrates theWidespread Occurrence of Gene Clusters Encoding Bacteriocins inCyanobacteria. PLoS ONE 6(7): e22384, hereby incorporated by referencein its entirety. Exemplary cyanobacteria bacteriocins are shown in Table1.2, as SEQ ID NO's 420, 422, 424, 426, 428, 30, 432, 434, 436, 438,440, 442, 444, 446, 448, and 450.

In some embodiments, the host cell itself is a microbial cell. In someembodiments, bacteriocins neutralize cells of a different species orstrain from the host cell. In some embodiments, bacteriocins neutralizecells of the same species or strain as the host cell if these cells lackan appropriate immunity modulator. As bacteriocins can mediateneutralization of both host and non-host microbial organisms, theskilled artisan will readily appreciate that a bacteriocin is distinctfrom poison-antidote systems (described in more detail herein), whichinvolve an endogenous mechanism by which a host microorganism canneutralize only itself. In other words, bacteriocins can neutralizecells other than the cell in which they are produced (for example,bacteriocins can be selected and/or engineered to act as an ecologicalniche protector), while poison molecules kill only the individual cellin which they are produced (for example, to act as suicidal systems).

A number of bacteriocins have been identified and characterized. Withoutbeing limited by any particular theory, exemplary bacteriocins can beclassified as “class I” bacteriocins, which typically undergopost-translational modification, and “class II” bacteriocins, which aretypically unmodified. Additionally, exemplary bacteriocins in each classcan be categorized into various subgroups, as summarized in Table 1.1,which is adapted from Cotter, P. D. et al. “Bacteriocins—a viablealternative to antibiotics” Nature Reviews Microbiology 11: 95-105,hereby incorporated by reference in its entirety.

Without being limited by any particular theory, bacteriocins can effectneutralization of a target microbial cell in a variety of ways. Forexample, a bacteriocin can permeablize a cell wall, thus depolarizingthe cell wall and interfering with respiration.

TABLE 1.1 Classification of Exemplary Bacteriocins Group Distinctivefeature Examples Class I (typically modified) MccC7-C51-type Iscovalently attached to a carboxy- MccC7-C51 bacteriocins terminalaspartic acid Lasso peptides Have a lasso structure MccJ25 Linear azole-or Possess heterocycles but not other MccB17 azoline-containingmodifications peptides Lantibiotics Possess lanthionine bridges Nisin,planosporicin, mersacidin, actagardine, mutacin 1140 Linaridins Have alinear structure and contain Cypemycin dehydrated amino acids ProteusinsContain multiple hydroxylations, Polytheonamide A epimerizations andmethylations Sactibiotics Contain sulphur-α-carbon linkages SubtilosinA, thuricin CD Patellamide-like Possess heterocycles and undergoPatellamide A cyanobactins macrocyclization Anacyclamide-like Cyclicpeptides consisting of Anacyclamide A10 cyanobactins proteinogenic aminoacids with prenyl attachments Thiopeptides Contain a central pyridine,Thiostrepton, nocathiacin dihydropyridine or piperidine ring as I,GE2270 A, philipimycin well as heterocycles Bottromycins Containmacrocyclic amidine, a Bottromycin A2 decarboxylated carboxy-terminalthiazole and carbon-methylated amino acids Glycocins Contain S-linkedglycopeptides Sublancin 168 Class II (typically unmodified or cyclic)IIa peptides (pediocin Possess a conserved YGNGV motif Pediocin PA-1,enterocin PA-1-like (in which N represents any amino CRL35,carnobacteriocin bacteriocins) acid) BM1 IIb peptides Two unmodifiedpeptides are required ABP118, lactacin F for activity IIc peptidesCyclic peptides Enterocin AS-48 IId peptides Unmodified, linear,non-pediocin-like, MccV, MccS, epidermicin single-peptide bacteriocinsNI01, lactococcin A IIe peptides Contain a serine-rich carboxy-terminalMccE492, MccM region with a non-ribosomal siderophore-type modification

A number of bacteriocins can be used in accordance with embodimentsherein. Exemplary bacteriocins are shown in Table 1.2. In someembodiments, at least one bacteriocin comprising a polypeptide sequenceof Table 1.2 is provided. As shown in Table 1.2, some bacteriocinsfunction as pairs of molecules. As such, it will be understood thatunless explicity stated otherwise, when a functional “bacteriocin” or“providing a bacteriocin,” or the like is discussed herein, functionalbacteriocin pairs are included along with bacteriocins that functionindividually. With reference to Table 1.2, “organisms of origin” listedin parentheses indicate alternative names and/or strain information fororganisms known the produce the indicated bacteriocin.

Embodiments herein also include peptides and proteins with identity tobacteriocins described in Table 1.2. The term “identity” is meant toinclude nucleic acid or protein sequence homology or three-dimensionalhomology. Several techniques exist to determine nucleic acid orpolypeptide sequence homology and/or three-dimensional homology topolypeptides. These methods are routinely employed to discover theextent of identity that one sequence, domain, or model has to a targetsequence, domain, or model. A vast range of functional bacteriocins canincorporate features of bacteriocins disclosed herein, thus providingfor a vast degree of identity to the bacteriocins in Table 1.2. In someembodiments, a bacteriocin has at least about 50% identity, for example,at least about 50%, 51%, 52%, 53%, 54%, 55%, 56%, 57%, 58%, 59%, 60%,61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%,75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%,89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identityto any one of the polypeptides of Table 1.2. Percent identity may bedetermined using the BLAST software (Altschul, S. F., et al. (1990)“Basic local alignment search tool.” J. Mol. Biol. 215:403-410,accessible on the world wide web at blast.ncbi.nlm.nih.gov) with thedefault parameters.

In some embodiments, a polynucleotide encoding a bacteriocin asdescribed herein is provided. In some embodiments, the polynucleotide iscomprised within an expression vector. In some embodiments, thepolynucleotide or expression vector is in a microbial cell. Exemplarypolynucleotide sequences encoding the polypeptides of table 1.2 areindicated in table 1.2. SEQ ID NOs: 341 to 419 (odd SEQ ID numbers)represent exemplary polynucleotides based on the reverse translation ofthe respective polypeptide. The skilled artisan will readily understandthat more than one polynucleotide can encode a particular polypeptide.For example, the genetic code is degenerate, and moreover, codon usagecan vary based on the particular organism in which the gene product isbeing expressed. In some embodiments, a polynucleotide encoding abacteriocin is selected based on the codon usage of the organismexpressing the bacteriocin. In some embodiments, a polynucleotideencoding a bacteriocin is codon optimized based on the particularorganism expressing the bacteriocin.

While the bacteriocins in Table 1.2 are naturally-occurring, the skilledartisan will appreciate that variants of the bacteriocins of Table 1.2,naturally-occurring bacteriocins other than the bacteriocins of Table1.2 or variants thereof, or synthetic bacteriocins can be used accordingto some embodiments herein. In some embodiments, such variants haveenhanced or decreased levels of cytotoxic or growth inhibition activityon the same or a different microorganism or species of microorganismrelative to the wild type protein. Several motifs have been recognizedas characteristic of bacteriocins. For example, the motif YGXGV (SEQ IDNO: 2), wherein X is any amino acid residue, is a N-terminal consensussequence characteristic of class IIa bacteriocins. Accordingly, in someembodiments, a synthetic bacteriocin comprises an N-terminal sequencewith at least about 50% identity to SEQ ID NO: 2, for example at leastabout 50%, 51%, 52%, 53%, 54%, 55%, 56%, 57%, 58%, 59%, 60%, 61%, 62%,63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%,77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%,91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to SEQ IDNO: 2. In some embodiments, a synthetic bacteriocin comprises aN-terminal sequence comprising SEQ ID NO: 2. Additionally, some classIIb bacteriocins comprise a GxxxG motif. Without being limited by anyparticular theory, it is believed that the GxxxG motif can mediateassociation between helical proteins in the cell membrane, for exampleto facilitate bacterioncin-mediated neutralization through cell membraneinteractions. As such, in some embodiments, the bacteriocin comprises amotif that facilitates interactions with the cell membrane. In someembodiments, the bacteriocin comprises a GxxxG motif. Optionally, thebacteriocin comprising a GxxxG motif can comprise a helical structure.In addition to structures described herein, “bacteriocin” as used hereinalso encompasses structures that have substantially the same effect onmicrobial cells as any of the bacteriocins explicitly provided herein.

It has been shown that fusion polypeptides comprising two or morebacteriocins or portions thereof can have neutralizing activity againsta broader range of microbial organisms than either individualbacteriocin. For example, it has been shown that a hybrid bacteriocin,Ent35-MccV (GKYYGNGVSCNKKGCSVDWGRAIGIIGNNSAANLATGGAAGWKSGGGASGRDIAMAIGTLSGQFVAGGIGAAAGGVAGGAIYDYASTHKPNPAMSPSGLGGTIKQKPEGIPSEAWNYAAGRLCNWSPNNLSDVCL, SEQ ID NO: 3), displays antimicrobial activityagainst pathogenic Gram-positive and Gram-negative bacteria (Acuñ a etal. (2012), FEBS Open Bio, 2: 12-19). It is noted that that Ent35-MccVfusion bacteriocin comprises, from N-terminus to C-terminus, anN-terminal glycine, Enterocin CRL35, a linker comprising three glycines,and a C-terminal Microcin V. It is contemplated herein that bacteriocinscan comprise fusions of two or more polypeptides having bacteriocinactivity. In some embodiments, a fusion polypeptide of two or morebacteriocins is provided. In some embodiments, the two or morebacteriocins comprise polypeptides from Table 1.2, or modificationsthereof. In some embodiments, the fusion polypeptide comprising of twoor more bacteriocins has a broader spectrum of activity than eitherindividual bacteriocin, for example having neutralizing activity againstmore microbial organisms, neutralizing activity under a broader range ofenvironmental conditions, and/or a higher efficiency of neutralizationactivity. In some embodiments, a fusion of two or more bacteriocins isprovided, for example two, three, four, five, six, seven, eight, nine,or ten bacteriocins. In some embodiments, two or more bacteriocinpolypeptides are fused to each other via a covalent bond, for example apeptide linkage. In some embodiments, a linker is positioned between thetwo bacteriocin polypeptides. In some embodiments, the linker comprisesone or glycines, for example about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11,12, 13, 14, 15, 16, 17, 18, 19, or 20 glycines. In some embodiments, thelinker is cleaved within the cell to produce the individual bacteriocinsincluded in the fusion protein. In some embodiments, a bacteriocin asprovided herein is modified to provide a desired spectrum of activityrelative to the unmodified bacteriocin. For example, the modifiedbacteriocin may have enhanced or decreased activity against the sameorganisms as the unmodified bacteriocin. Alternatively, the modifiedbacteriocin may have enhanced activity against an organism against whichthe unmodified bacteriocin has less activity or no activity.

TABLE 1.2 Exemplary Bacteriocins Poly- nucleotide Poly- SEQ peptidePolypeptide Organism of ID Polynucleotide SEQ ID NO: Name Class Sequenceorigin NO: Sequence 4 Acidocin Unclassified MISSHQKTL Lactobacillus 5ATGATTTCATC 8912 TDKELALISG acidophilus TCATCAAAAA GKTHYPTNA ACGTTAACTGWKSLWKGF ATAAAGAATT WESLRYTDGF AGCATTAATTT CTGGGGGGAA AACGCACTACCCGACTAATG CATGGAAAAG TCTTTGGAAA GGTTTCTGGG AAAGCCTTCG TTATACTGACGGTTTTTAG 6 Acidocin A class MISMISSHQ Lactobacillus 7 ATGATTTCAATIIA/YG KTLTDKELA acidophilus GATTTCATCTC NGV LISGGKTYY ATCAAAAAACGTNGVHCTK GTTAACTGAT KSLWGKVRL AAAGAATTAG KNVIPGTLC CATTAATTTCTRKQSLPIKQ GGGGGGAAAA DLKILLGWA CGTACTATGG TGAFGKTFH TACTAATGGTGTGCATTGTA CTAAAAAGAG TCTTTGGGGT AAAGTACGCT TAAAAAACGT GATTCCTGGAACTCTTTGTCG TAAGCAATCG TTGCCGATCA AACAGGATTT AAAAATTTTA CTGGGCTGGGCTACAGGTGC TTTTGGCAAG ACATTTCATTAA 8 Acidocin Unclassified MDKKTKILFLactobacillus 9 ATGGATAAGA B (AcdB) EVLYIICIIGP acidophilus AAACAAAAATQFILFVTAKN ATTATTTGAA NMYQLVGSF GTATTATACAT VGIVWFSYIF CATCTGTATAWYIFFKQHK ATAGGCCCTC KM AATTTATATTA TTTGTGACTGC AAAAAACAAT ATGTATCAGTTGGTGGGTTC GTTTGTTGGA ATAGTATGGT TTTCGTATATT TTTTGGTATAT TTTTTTCAAACAACATAAAAA AATGTAG 10 Acidocin Unclassified MALKTLEKH Lactobacillus 11ATGGCTTTAA LF221B ELRNVMGG gasseri AAACATTAGA (Gassericin NKWGNAVIAAAACATGAA K7 B) GAATGATRG TTAAGAAATG VSWCRGFGP TAATGGGTGG WGMTACALAAACAAGTGG GGAAIGGYL GGGAATGCTG GYKSN TAATAGGAGC TGCTACGGGA GCTACTCGCGGAGTAAGTTG GTGCAGAGGA TTCGGACCAT GGGGAATGAC TGCCTGTGCG TTAGGAGGTGCTGCAATTGG AGGATATCTG GGATATAAGA GTAATTAA 12 Aureocin UnclassifiedMSWLNFLK Staphylococcus 13 ATGAGTTGGT A53 YIAKYGKKA aureus TAAATTTTTTAVSAAWKYK AAATACATCG GKVLEWLN CTAAATATGG VGPTLEWV CAAAAAAGCG WQKLKKIAGLGTATCTGCTG CTTGGAAGTA CAAAGGTAAA GTATTAGAAT GGCTTAATGT TGGTCCTACTCTTGAATGGGT ATGGCAAAAA TTAAAGAAAA TTGCTGGATT ATAA 14 Avicin A classMTRSKKLNL Enterococcus 15 ATGACAAGAT IIA/YG REMKNVVG avium CAAAAAAATTNGV GTYYGNGVS (Streptococcus AAATTTACGC CNKKGCSVD avium) GAAATGAAGAWGKAISIIGN ATGTTGTTGG NSAANLATG TGGTACCTAC GAAGWKS TATGGAAATGGTGTATCTTGT AACAAGAAAG GCTGTTCAGTT GACTGGGGCA AAGCCATCAG TATTATAGGAAATAATTCCG CAGCAAACTT AGCAACTGGT GGTGCTGCTG GTTGGAAGTC ATAA 16Bacteriocin Unclassified MKKKLVICG Enterococcus 17 ATGAAAAAGA 31IIGIGFTALG faecalis AATTAGTTATT TNVEAATYY (Streptococcus TGTGGCATTAGNGLYCNK faecalis) TTGGGATTGG QKCWVDWN TTTTACAGCAT KASREIGKII TAGGAACAAAVNGWVQHG TGTAGAAGCT PWAPR GCTACGTATT ACGGAAATGG TTTATATTGTA ATAAGCAAAAATGTTGGGTA GACTGGAATA AAGCTTCAAG GGAAATTGGA AAAATTATTG TTAATGGTTGGGTACAACAT GGCCCTTGGG CTCCTAGATAG 18 Bacteriocin Unclassified MKEQNSFNLLactococcus 19 ATGAAAGAAC J46 LQEVTESEL lactis AAAACTCTTTT DLILGAKGGAATCTTCTTCA SGVIHTISHE AGAAGTGACA VIYNSWNFV GAAAGTGAAT FTCCS TGGACCTTATTTTAGGTGCAA AAGGCGGCAG TGGAGTTATT CATACAATTTC TCATGAAGTA ATATATAATAGCTGGAACTT TGTATTTACTT GCTGCTCTTAA 20 Bacteriocin class IIa MKKKVLKHEnterococcus 21 ATGAAAAAGA T8 CVILGILGTC faecium AAGTATTAAA LAGIGTGIKV(Streptococcus ACATTGTGTT DAATYYGN faecium) ATTCTAGGAA GLYCNKEKCTATTAGGAAC WVDWNQAK TTGTCTAGCTG GEIGKIIVNG GCATCGGTAC WVNHGPWAAGGAATAAAA PRR GTTGATGCAG CTACTTACTAT GGAAATGGTC TTTATTGTAAC AAAGAAAAATGTTGGGTAGA TTGGAATCAA GCTAAAGGAG AAATTGGAAA AATTATTGTTA ATGGTTGGGTTAATCATGGT CCATGGGCAC CTAGAAGGTAG 22 Boticin B Unclassified MQKPEIISADClostridium 23 ATGCAAAAAC LGLCAVNEF botulinum CAGAAATTAT VALAAIPGGTAGTGCTGAT AATFAVCQ TTAGGGCTTT MPNLDEIVS GTGCAGTTAA NAAYV TGAATTTGTAGCTCTTGCTGC CATTCCTGGT GGTGCTGCTA CATTTGCAGT ATGCCAAATG CCAAACTTGGATGAGATTGT TAGTAATGCA GCATATGTTT AA 24 Bovicin Lantibiotic MMNATENQIStreptococcus 25 ATGATGAATG HJ50 FVETVSDQE equinus CTACTGAAAA LEMLIGGAD(Streptococcus CCAAATTTTTG RGWIKTLTK bovis) TTGAGACTGT DCPNVISSICGAGTGACCAA AGTIITACKN GAATTAGAAA CA TGTTAATTGGT GGTGCAGATC GTGGATGGATTAAGACTTTA ACAAAAGATT GTCCAAATGT AATTTCTTCAA TTTGTGCAGG TACAATTATTACAGCTTGTAA AAATTGTGCT TAA 26 Brochocin-c Unclassified MHKVKKLNBrochothrix 27 ATGCACAAGG NQELQQIVG campestris TAAAAAAATT GYSSKDCLKAAACAATCAA DIGKGIGAG GAGTTACAAC TVAGAAGG AGATCGTGGG GLAAGLGAI AGGTTACAGTPGAFVGAHF TCAAAAGATT GVIGGSAACI GTCTAAAAGA GGLLGN TATTGGTAAA GGAATTGGTGCTGGTACAGT AGCTGGGGCA GCCGGCGGTG GCCTAGCTGC AGGATTAGGT GCTATCCCAGGAGCATTCGT TGGAGCACAT TTTGGAGTAA TCGGCGGATC TGCCGCATGC ATTGGTGGATTATTAGGTAA CTAG 28 Butyrivibriocin Unclassified MSKKQIMSN Butyrivibrio29 ATGAGTAAAA AR10 CISIALLIALI fibrisolvens AACAAATTAT PNIYFIADKMGAGTAACTGT GIQLAPAWY ATATCAATTG QDIVNWVSA CATTATTAATA GGTLTTGFAIGCACTAATTC IVGVTVPAW CTAATATCTAT IAEAAAAFGI TTTATTGCAG ASA ATAAAATGGGAATTCAGTTA GCACCTGCTT GGTATCAAGA TATTGTGAATT GGGTATCTGC TGGTGGAACACTTACTACTG GTTTTGCGATT ATTGTAGGAG TTACAGTACC GGCATGGATA GCAGAAGCAGCTGCAGCTTTT GGTATAGCTT CAGCATGA 30 Butyrivibriocin Lantibiotic MNKELNALTButyrivibrio 31 ATGAACAAAG OR79 NPIDEKELEQ fibrisolvens AACTTAATGCILGGGNGVI ACTTACAAAT KTISHECHM CCTATTGACG NTWQFIFTC AGAAGGAGCT CSTGAGCAGATC CTCGGTGGTG GCAATGGTGT CATCAAGACA ATCAGCCACG AGTGCCACATGAACACATGG CAGTTCATTTT CACATGTTGC TCTTAA 32 Carnobacteriocin classMNSVKELN Carnobacterium 33 ATGAATAGCG B2 IIA/YG VKEMKQLH maltaromaticumTAAAAGAATT (Carnocin NGV GGVNYGNG (Carnobacterium AAACGTGAAA CP52)VSCSKTKCS piscicola) GAAATGAAAC VNWGQAFQ AATTACACGG ERYTAGINSFTGGAGTAAAT VSGVASGAG TATGGTAATG SIGRRP GTGTTTCTTGC AGTAAAACAA AATGTTCAGTTAACTGGGGA CAAGCCTTTC AAGAAAGATA CACAGCTGGA ATTAACTCATT TGTAAGTGGAGTCGCTTCTG GGGCAGGATC CATTGGTAGG AGACCGTAA 34 Carnobacteriocin classMKSVKELNK Carnobacterium 35 ATGAAAAGCG BM1 IIA/YG KEMQQINGGmaltaromaticum TTAAAGAACT (Carnobacteriocin NGV AISYGNGVY(Carnobacterium AAATAAAAAA B1) CNKEKCWV piscicola) GAAATGCAAC NKAENKQAIAAATTAATGG TGIVIGGWA TGGAGCTATC SSLAGMGH TCTTATGGCA ATGGTGTTTATTGTAACAAAG AGAAATGTTG GGTAAACAAG GCAGAAAACA AACAAGCTAT TACTGGAATAGTTATCGGTG GATGGGCTTC TAGTTTAGCA GGAATGGGAC ATTAA 36 Carnobacteriocin-Aclass IIc, MNNVKELSI Carnobacterium 37 ATGAATAATG (Piscicolin- nonKEMQQVTG maltaromaticum TAAAAGAGTT 61) subgrouped GDQMSDGV(Carnobacterium AAGTATTAAA bacteriocins NYGKGSSLS piscicola) GAAATGCAAC(problematic) KGGAKCGL AAGTTACTGG GIVGGLATIP TGGAGACCAA SGPLGWLAGATGTCAGATG AAGVINSCMK GTGTAAATTA TGGAAAAGGC TCTAGCTTATC AAAAGGTGGTGCCAAATGTG GTTTAGGGAT CGTCGGCGGA TTAGCTACTAT CCCTTCAGGT CCTTTAGGCTGGTTAGCCGG AGCAGCAGGT GTAATTAATA GCTGTATGAA ATAA 38 Carnocyclin-AUnclassified MLYELVAY Carnobacterium 39 ATGTTATATG GIAQGTAEKmaltaromaticum AATTAGTTGC VVSLINAGL (Carnobacterium ATATGGTATCTVGSIISILG piscicola) GCACAAGGTA GVTVGLSGV CAGCTGAAAA FTAVKAAIAGGTTGTAAGT KQGIKKAIQL CTAATTAACG CAGGTTTAAC AGTAGGGTCT ATTATTTCAATTTTGGGTGGG GTCACAGTCG GTTTATCAGG TGTCTTCACA GCAGTTAAAG CAGCAATTGCTAAACAAGGA ATAAAAAAAG CAATTCAATT ATAA 40 Carocin D UnclassifiedMIKYRLYAP Pectobacterium 41 ATGATTAAAT NDGDTMTV carotovorum ACCGTTTATATSGGGGWVS subsp. GCTCCAAATG NDDRKGGN carotovorum ATGGAGACAC DRDNGKGG(Erwinia CATGACAGTG SAVDFSKNP carotovora AGTGGTGGTG EKQAIVNPY subsp.GTGGTTGGGT LAIAIPMPVY carotovora) TTCAAACGAT PLYGKLGFTI GATCGCAAAGNTTAIETELA GTGGTAATGA NVRAAINTK CAGGGACAAT LATLSAVIGR GGCAAAGGTGSLPVVGRVF GTTCTGCCGTT GVTAAGMW GATTTTAGTA PSSTAPSSLD AAAATCCAGASIYNQAHQQ AAAGCAGGCT ALAQLAAQQ ATCGTTAATCC GVLNKGYN CTATTTGGCA VTAMPAGFVATCGCGATAC SSLPVSEIKS CGATGCCGGT LPTAPASLLA CTACCCTCTTT QSVINTELSQATGGAAAGCT RQLALTQPT AGGGTTCACA TNAPVANIP ATAAATACGA VVKAEKTA CGGCAATTGAMPGVYSAKI GACTGAACTC IAGEPAFQIK GCAAATGTCA VDNTKPALA GAGCAGCAATQNPPKVKDD TAACACTAAA IQVSSFLSSP CTTGCAACAC VADTHHAFI TCAGTGCAGTDFGSDHEPV GATTGGCAGA YVSLSKIVT TCACTTCCGGT AEEEKKQVE CGTTGGGCGGEAKRREQEW GTATTTGGTG LLRHPITAAE TTACTGCCGC RKLTEIRQVI CGGAATGTGGSFAQQLKES CCTTCTAGTAC SVATISEKTK CGCTCCCAGT TVAVYQEQ AGTCTCGATT VNTAAKNRCTATATACAA DNFYNQNR TCAAGCACAT GLLSAGITG CAGCAGGCTT GPGYPIYLA TAGCCCAGTTLWQTMNNF AGCTGCTCAA HQAYFRANN CAGGGAGTAT ALEQESHVL TAAATAAAGG NLARSDLAKGTATAACGTT AEQLLAENN ACAGCAATGC RLQVETERT CTGCAGGTTT LAEEKEIKRCGTCAGCAGT NRVNVSTFG TTGCCTGTTAG TVQTQLSKL TGAAATCAAA LSDFYAVTSTCATTGCCAA LSQSVPSGA CAGCTCCCGC LASFSYNPQ CAGTTTACTG GMIGSGKIVGCACAAAGTG GKDVDVLFS TGATTAATAC IPVKDIPGYK CGAACTTTCCC SPINLDDLAKAGCGTCAACT KNGSLDLPIR GGCTCTTACTC LAFSDENGE AGCCCACGAC RVLRAFKADGAATGCACCA SLRIPSSVRG GTCGCGAATA VAGSYDKNT TTCCCGTAGTT GIFSAEIDGVAAAGCAGAGA SSRLVLENP AAACAGCAAT AFPPTGNVG GCCAGGTGTG NTGNTAPDYTATTCAGCGA KALLNTGVD AAATTATTGCT VKPVDKITV GGTGAGCCTG TVTPVADPVCATTCCAAAT DIDDYIIWLP CAAGGTCGAT TASGSGVEPI AATACCAAAC YVVFNSNPYCTGCTTTGGC GGTEKGKYS ACAGAATCCG KRYYNPDKA CCGAAAGTAA GGPILELDWAAGATGATAT KNVKIDHAG TCAGGTATCTT VDNVKLHT CTTTCCTTTCC GRFKASVENTCGCCAGTAG KVMIERLENI CTGATACGCA LNGQITATD CCATGCATTTA TDKRFYTHETTGATTTTGGC LRELNRYRN AGCGATCATG LGIKDGEVP AACCGGTATA SSIQEESAVCGTGTCTCTTT WNDTHTAT CAAAGATCGT LEDYKINEK GACAGCCGAG EQPLYTDAAGAGGAGAAAA LQAAYEQEL AACAGGTTGA KDALGGKHG AGAGGCCAAG CGCCGTGAGCAGGAGTGGTT GTTGCGTCAT CCAATTACAG CTGCGGAGCG AAAATTAACT GAAATCCGCCAAGTGATCTC TTTTGCTCAAC AGCTAAAAGA AAGCTCTGTC GCAACCATTT CAGAAAAAACTAAAACTGTT GCGGTTTACC AAGAACAGGT GAATACCGCT GCAAAAAATC GCGACAATTTTTATAATCAA AATAGAGGTC TGTTAAGTGC GGGTATAACT GGGGGACCGG GATATCCTATTTATCTTGCTTT ATGGCAAACG ATGAATAACT TTCATCAGGC TTATTTCAGA GCAAATAATGCATTGGAACA AGAGAGTCAT GTTCTGAACC TGGCTCGTTCT GATCTGGCTA AGGCTGAGCAATTGCTTGCTG AGAATAATCG ACTTCAGGTT GAAACGGAGC GAACGCTTGC CGAAGAAAAAGAGATAAAAC GCAACAGGGT TAATGTATCA ACATTTGGCA CAGTGCAAAC TCAACTTAGTAAATTGCTGT CAGATTTTTAT GCTGTTACAT CACTTTCCCAA AGTGTTCCTTC GGGGGCATTAGCCTCTTTTTC ATATAATCCA CAAGGGATGA TTGGCAGCGG TAAGATTGTT GGGAAGGATGTCGATGTTTTA TTTTCCATCCC AGTAAAAGAT ATTCCGGGAT ATAAATCTCCT ATTAACTTGGACGATTTAGC CAAGAAAAAT GGAAGTCTGG ATCTTCCCATT CGTCTGGCAT TTTCTGATGAGAATGGAGAA AGGGTTCTTC GGGCATTCAA AGCGGATAGT CTGCGAATCC CTTCGAGTGTCAGAGGTGTA GCGGGCAGTT ATGACAAAAA TACGGGTATT TTTAGTGCAG AAATTGATGGTGTTTCATCTC GCCTTGTACT GGAAAACCCA GCGTTTCCTCC GACCGGAAAT GTCGGTAATACGGGTAATAC TGCACCTGAC TATAAAGCAT TACTGAATAC TGGTGTTGAT GTTAAACCTGTTGATAAAAT CACAGTTACG GTAACACCAG TTGCTGATCC AGTGGATATT GATGACTATATAATCTGGTT GCCAACTGCG TCTGGTTCTG GCGTGGAACC CATTTATGTCG TGTTTAACAGTAATCCGTAT GGTGGGACGG AAAAAGGAAA ATATAGCAAA CGTTATTATAA TCCAGATAAGGCAGGCGGTC CGATCTTGGA GCTGGATTGG AAAAACGTTA AGATTGACCA TGCAGGTGTGGACAATGTTA AATTACACAC AGGGCGTTTC AAAGCGTCGG TTGAAAACAA AGTGATGATTGAACGTTTGG AAAACATACT GAATGGTCAA ATCACGGCCA CGGATACTGA CAAGCGATTCTATACGCATG AATTAAGAGA GTTAAACCGC TACAGAAATT TAGGCATCAA AGACGGTGAAGTGCCTAGTA GCATTCAAGA AGAAAGCGCT GTTTGGAACG ACACACACAC AGCGACGCTTGAAGACTACA AAATTAATGA GAAAGAGCAA CCGTTGTACA CTGATGCTGC TTTGCAGGCAGCCTACGAAC AGGAACTCAA AGACGCATTA GGAGGGAAAC ATGGCTAA 42 Cerein 7BUnclassified MENLQMLT Bacillus 43 ATGGAAAACT EEELMEIEG cereus TACAAATGTTGGWWNSWG AACTGAAGAA KCVAGTIGG GAATTAATGG AGTGGLGGA AAATTGAAGG AAGSAVPVITGGAGGCTGG GTGIGGAIG TGGAATAGCT GVSGGLTGA GGGGTAAATG ATFC TGTTGCTGGAACTATCGGTG GAGCTGGAAC TGGTGGTTTA GGTGGAGCTG CTGCAGGTTC AGCTGTTCCGGTTATTGGTA CTGGTATTGG TGGCGCTATT GGTGGAGTTA GCGGTGGCCT TACAGGTGCAGCTACTTTTTG CTAA 44 Cinnamycin Lantibiotic MTASILQQS Streptoverticillium45 ATGACCGCTT (Lanthiopeptin) VVDADFRAA griseoverticillatum CCATTCTTCAGLLENPAAFG CAGTCCGTCG ASAAALPTP TGGACGCCGA VEAQDQASL CTTCCGCGCG DFWTKDIAAGCGCTGCTTG TEAFACRQS AGAACCCCGC CSFGPFTFVC CGCCTTCGGC DGNTK GCTTCCGCCGCGGCCCTGCC CACGCCCGTC GAGGCCCAGG ACCAGGCGTC CCTTGACTTCT GGACCAAGGACATCGCCGCC ACGGAAGCCT TCGCCTGCCG CCAGAGCTGC AGCTTCGGCC CGTTCACCTTCGTGTGCGACG GCAACACCAA GTAA 46 Circularin A Unclassified MSLLALVAGGeobacillus 47 ATGAGTTTGC TLGVSQSIAT kaustophilus TGGCGCTTGT TVVSIVLTGS(strain TGCCGGGACG TLISIILGITAI HTA426) CTCGGCGTGT LSGGVDAIL CACAGTCAATEIGWSAFVA CGCGACGACG TVKKIVAER GTTGTTTCGAT GKAAAIAW TGTGTTGACCGGCTCCACTC TCATTTCTATT ATTCTTGGGA TCACCGCTATT TTGTCAGGTG GAGTCGACGCCATTTTGGAA ATTGGGTGGT CAGCTTTTGTC GCGACGGTGA AAAAAATAGT GGCGGAACGAGGAAAAGCGG CAGCGATTGC ATGGTAA 48 Closticin Unclassified MRKVFLRSIIClostridium 49 TTGAGAAAAG 574 STLVMCAFV tyrobutyricum TATTTTTAAGASSSFSVNAD TCAATAATTTC ESKPNDEKII AACATTAGTT NNIENVTTT ATGTGTGCATKDIVKSNKN TTGTTTCAAGC NIVYLDEGV AGCTTTTCAGT MSIPLSGRKP AAATGCGGATIAIKDDNNK GAAAGCAAAC EDLTVTLPIK CAAATGATGA NTGDISKISS AAAAATAATTNGTILYKNN AATAACATAG SSNSSNIALQ AAAACGTTAC PKNDGFKAL TACTACTAAAININDKLAN GATATTGTAA KEYEFTFNL AAAGTAATAA PKNSKLISAA AAATAATATTTYLGKEYDT GTATATTTAG KEVFVVDKN ATGAAGGTGT NIITSIISPAW AATGAGTATTAKDANGHN CCATTGTCTG VSTYYKIVS GGAGAAAACC NNKLVQVV CATTGCTATTA EFTENTAFPAAGATGATAA VVADPNWT TAATAAAGAA KIGKCAGSIA GATTTAACTG WAIGSGLFGTTACATTACCT GAKLIKIKKY ATTAAGAATA IAELGGLQK CTGGAGATAT AAKLLVGATATCTAAAATT TWEEKLHAG AGTAGTAATG GYALINLAA GTACTATTCTG ELTGVAGIQTATAAAAATA ANCF ATAGTAGTAA TTCATCTAATA TAGCTTTACA ACCTAAAAAT GATGGATTTAAGGCTTTAAT AAATATTAAT GATAAGTTAG CTAATAAAGA ATATGAATTT ACATTTAATTTACCCAAAAAC AGTAAATTAA TTAGTGCTGC CACATATTTG GGTAAAGAAT ATGATACAAAAGAAGTATTT GTAGTAGACA AAAATAATAT AATTACGAGT ATTATTAGTCC AGCTTGGGCTAAAGATGCAA ATGGACATAA TGTTTCTACTT ATTATAAGAT AGTATCGAAT AATAAATTAGTACAAGTTGT TGAATTCACA GAAAATACTG CATTCCCGGT GGTAGCTGAT CCTAATTGGACTAAAATTGG GAAATGCGCT GGGTCAATAG CATGGGCTAT AGGTTCTGGC CTTTTTGGTGGAGCAAAGCTA ATTAAAATAA AAAAATATAT AGCAGAGCTT GGAGGACTTC AAAAAGCAGCTAAATTATTA GTTGGTGCAA CCACTTGGGA AGAAAAATTA CACGCAGGCG GTTATGCATTAATTAACTTA GCTGCTGAGC TAACAGGTGT AGCAGGTATA CAAGCAAATT GTTTTTAA 50Coagulin A Unclassified MKKIEKLTE Bacillus 51 ATGAAAAAAA KEMANIIGGcoagulans TTGAAAAATT KYYGNGVT AACTGAAAAA CGKHSCSVD GAAATGGCCA WGKATTCIIATATCATTGG NNGAMAWA TGGTAAATAC TGGHQGTH TACGGTAATG KC GGGTTACTTGTGGCAAACAT TCCTGCTCTGT TGACTGGGGT AAGGCTACCA CCTGCATAAT CAATAATGGAGCTATGGCAT GGGCTACTGG TGGACATCAA GGTACTCATA AATGCTAG 52 Colicin-10Unclassified MDKVTDNSP Escherichia 53 ATGGATAAAG DVESTESTE coliTCACTGATAA GSFPTVGVD TTCTCCAGAT TGDTITATL GTGGAGAGCA ATGTENVGGCAGAATCTAC GGGAFGGAS TGAGGGGTCA ESSAAIHATA TTCCCAACTGT KWSTAQLKKTGGGGTTGAT HQAEQAAR ACTGGCGATA AAAAEAALA CGATTACAGC KAKSQRDAL GACGCTTGCATQRLKDIVN ACTGGAACTG DALRANAAR AAAATGTTGG SPSVTDLAH TGGAGGCGGT ANNMAMQAGGAGCATTTG EAERLRLAK GTGGGGCCAG AEQKAREEA TGAAAGTTCT EAAEKALREGCTGCGATAC AERQRDEIA ATGCAACCGC RQQAETAHL TAAATGGTCT LAMAEAAEAACCGCGCAGT EKNRQDSLD TGAAAAAACA EEHRAVEVA TCAGGCTGAA EKKLAEAKACAGGCTGCCC ELAKAESDV GTGCTGCTGC QSKQAIVSR GGCTGAGGCA VAGELENAQGCATTGGCAA KSVDVKVTG AAGCGAAATC FPGWRDVQ TCAGCGTGAT KKLERQLQD GCCCTGACTCKKNEYSSVT AACGTCTCAA NALNSAVSI GGATATTGTT RDAKKTEVQ AATGACGCTT NAEIKLKEATACGTGCTAA KDALEKSQV TGCCGCTCGT KDSVDTMV AGTCCATCAG GFYQYITEQTAACTGACCTT YGEKYSRIA GCTCATGCCA QDLAEKAKG ATAATATGGC SKFNSVDEAAATGCAGGCA LAAFEKYKN GAGGCTGAGC VLDKKFSKV GTTTGCGCCTT DRDDIFNALGCGAAGGCAG ESITYDEWA AGCAAAAAGC KHLEKISRAL CCGTGAAGAA KVTGYLSFGGCTGAAGCAG YDVWDGTL CAGAAAAAGC KGLKTGDW GCTCCGGGAA KPLFVTLEKS GCAGAACGCCAVDFGVAKI AACGTGATGA VALMFSFIV GATTGCCCGC GAPLGFWGI CAACAGGCTGAIITGIVSSYI AAACCGCGCA GDDELNKLN TTTGTTAGCA ELLGI ATGGCGGAGG CAGCAGAGGCTGAGAAAAAT CGACAGGATT CTCTTGATGA AGAGCATCGG GCTGTGGAAG TGGCAGAGAAGAAGCTGGCT GAGGCTAAAG CTGAACTGGC GAAGGCCGAA AGCGATGTAC AGAGTAAGCAAGCGATTGTT TCCAGAGTTG CAGGGGAGCT TGAAAACGCT CAAAAAAGTG TTGATGTGAAGGTTACCGGA TTTCCTGGATG GCGTGATGTT CAGAAAAAAC TGGAGAGACA ATTGCAGGATAAGAAGAATG AATATTCGTC AGTGACGAAT GCTCTTAATTC TGCTGTTAGC ATTAGAGATGCTAAAAAAAC AGAAGTTCAG AATGCTGAGA TAAAATTAAA AGAAGCTAAG GATGCTCTTGAGAAGAGTCA GGTAAAAGAC TCTGTTGATAC TATGGTTGGG TTTTATCAATA TATAACCGAACAATATGGGG AAAAATATTC CAGAATAGCT CAGGATTTAG CTGAAAAGGC GAAGGGTAGTAAATTTAATA GTGTTGATGA AGCACTTGCT GCATTTGAAA AGTATAAAAA TGTACTGGATAAGAAATTCA GTAAGGTTGA TAGGGATGAT ATTTTTAATGC TTTAGAGTCT ATTACTTATGATGAGTGGGCC AAGCATCTAG AAAAGATCTC TAGGGCTCTT AAGGTTACTG GATATTTGTCTTTCGGGTATG ATGTATGGGA TGGTACCCTA AAGGGATTAA AAACAGGAGA CTGGAAGCCTTTATTTGTCAC TCTGGAGAAG AGCGCGGTAG ATTTCGGCGT GGCAAAAATT GTGGCATTAATGTTTAGTTTT ATTGTTGGTG CGCCTCTTGG CTTCTGGGGA ATTGCAATTAT CACAGGTATTGTTTCTTCTTA CATAGGGGAT GATGAGTTGA ACAAGCTTAA TGAATTACTA GGTATTTAA 54Colicin- Unclassified METAVAYY Escherichia 55 ATGGAAACCG E1 KDGVPYDDcoli CGGTAGCGTA KGQVIITLLN CTATAAAGAT GTPDGSGSG GGTGTTCCTTA GGGGKGGSTGATGATAAG KSESSAAIHA GGACAGGTAA TAKWSTAQL TTATTACTCTT KKTQAEQAATTGAATGGTA RAKAAAEAQ CTCCTGACGG AKAKANRD GAGTGGCTCT ALTQRLKDI GGCGGCGGAGVNEALRHNA GTGGAAAAGG SRTPSATELA AGGCAGTAAA HANNAAMQ AGTGAAAGTT AEDERLRLACTGCAGCTAT KAEEKARKE TCATGCAACT AEAAEKAFQ GCTAAATGGT EAEQRRKEICTACTGCTCA EREKAETER ATTAAAGAAA QLKLAEAEE ACACAGGCAG KRLAALSEEAGCAGGCTGC AKAVEIAQK CCGGGCAAAA KLSAAQSEV GCTGCAGCGG VKMDGEIKTAAGCACAGGC LNSRLSSSIH GAAAGCAAAG ARDAEMKTL GCAAACAGGG AGKRNELAQATGCGCTGAC ASAKYKELD TCAGCGCCTG ELVKKLSPR AAGGATATCG ANDPLQNRPTGAATGAGGC FFEATRRRV TCTTCGTCACA GAGKIREEK ATGCCTCACG QKQVTASETTACGCCTTCA RINRINADIT GCAACAGAGC QIQKAISQVS TTGCTCATGCT NNRNAGIARAATAATGCAG VHEAEENLK CTATGCAGGC KAQNNLLNS GGAAGACGAG QIKDAVDATCGTTTGCGCCT VSFYQTLTE TGCGAAAGCA KYGEKYSK GAAGAAAAAG MAQELADKSCCCGTAAAGA KGKKIGNVN AGCGGAAGCA EALAAFEKY GCAGAAAAGG KDVLNKKFSCTTTTCAGGA KADRDAIFN AGCAGAACAA ALASVKYDD CGACGTAAAG WAKHLDQF AGATTGAACGAKYLKITGH GGAGAAGGCT VSFGYDVVS GAAACAGAAC DILKIKDTGD GCCAGTTGAAWKPLFLTLE ACTGGCTGAA KKAADAGVS GCTGAAGAGA YVVALLFSL AACGACTGGC LAGTTLGIWTGCATTGAGT GIAIVTGILC GAAGAAGCTA SYIDKNKLN AAGCTGTTGA TINEVLGIGATCGCCCAA AAAAAACTTT CTGCTGCACA ATCTGAAGTG GTGAAAATGG ATGGAGAGATTAAGACTCTC AATTCTCGTTT AAGCTCCAGT ATCCATGCCC GTGATGCAGA AATGAAAACGCTCGCTGGAA AACGAAATGA ACTGGCTCAG GCATCCGCTA AATATAAAGA ACTGGATGAGCTGGTCAAAA AACTATCACC AAGAGCCAAT GATCCGCTTC AGAACCGTCC TTTTTTTGAAGCAACCAGACG ACGGGTTGGG GCCGGTAAGA TTAGAGAAGA AAAACAAAAA CAGGTAACAGCATCAGAAAC ACGTATTAAC CGGATAAATG CTGATATAAC TCAGATCCAG AAGGCTATTTCTCAGGTCAG TAATAATCGT AATGCCGGTA TCGCTCGTGTT CATGAAGCTG AAGAAAATTTGAAAAAAGCA CAGAATAATC TCCTTAATTCA CAGATTAAGG ATGCTGTTGA TGCAACAGTTAGCTTTTATCA AACGCTGACT GAAAAATATG GTGAAAAATA TTCGAAAATG GCACAGGAACTTGCTGATAA GTCTAAAGGT AAGAAAATCG GCAATGTGAA TGAAGCTCTC GCTGCTTTTGAAAAATACAAG GATGTTTTAA ATAAGAAATT CAGCAAAGCC GATCGTGATG CTATTTTTAATGCGTTGGCAT CGGTGAAGTA TGATGACTGG GCTAAACATT TAGATCAGTT TGCCAAGTACTTGAAGATTA CGGGGCATGT TTCTTTTGGAT ATGATGTGGT ATCTGATATCC TAAAAATTAAGGATACAGGT GACTGGAAGC CACTATTTCTT ACATTAGAGA AGAAAGCTGC AGATGCAGGGGTGAGTTATG TTGTTGCTTTA CTTTTTAGCTT GCTTGCTGGA ACTACATTAG GTATTTGGGGTATTGCTATTG TTACAGGAAT TCTATGCTCCT ATATTGATAA GAATAAACTT AATACTATAAATGAGGTGTT AGGGATTTAA 56 Colicin-Ia Unclassified MSDPVRITN Escherichia57 ATGTCTGACC PGAESLGYD coli CTGTACGTATT SDGHEIMAV ACAAATCCCG DIYVNPPRVGTGCAGAATC DVFHGTPPA GCTGGGGTAT WSSFGNKTI GATTCAGATG WGGNEWVD GCCATGAAATDSPTRSDIEK TATGGCCGTT RDKEITAYK GATATTTATGT NTLSAQQKE AAACCCTCCANENKRTEAG CGTGTCGATG KRLSAAIAA TCTTTCATGGT REKDENTLK ACCCCGCCTGTLRAGNADA CATGGAGTTC ADITRQEFRL CTTCGGGAAC LQAELREYG AAAACCATCTFRTEIAGYD GGGGCGGAAA ALRLHTESR CGAGTGGGTT MLFADADSL GATGATTCCCRISPREARSL CAACCCGAAG IEQAEKRQK TGATATCGAA DAQNADKK AAAAGGGACA AADMLAEYAGGAAATCAC ERRKGILDT AGCGTACAAA RLSELEKNG AACACGCTCA GAALAVLDAGCGCGCAGCA QQARLLGQQ GAAAGAGAAT TRNDRAISE GAGAATAAGC ARNKLSSVTGTACTGAAGC ESLNTARNA CGGAAAACGC LTRAEQQLT CTCTCTGCGG QQKNTPDGKCGATTGCTGC TIVSPEKFPG AAGGGAAAAA RSSTNHSIVV GATGAAAACA SGDPRFAGTICACTGAAAAC KITTSAVIDN ACTCCGTGCC RANLNYLLS GGAAACGCAG HSGLDYKRNATGCCGCTGA ILNDRNPVV TATTACACGA TEDVEGDKK CAGGAGTTCA IYNAEVAEWGACTCCTGCA DKLRQRLLD GGCAGAGCTG ARNKITSAES AGAGAATACG AVNSARNNLGATTCCGTAC SARTNEQKH TGAAATCGCC ANDALNALL GGATATGACG KEKENIRNQCCCTCCGGCT LSGINQKIAE GCATACAGAG EKRKQDELK AGCCGGATGC ATKDAINFTTGTTTGCTGAT TEFLKSVSE GCTGATTCTCT KYGAKAEQL TCGTATATCTC AREMAGQACCCGGGAGGC KGKKIRNVE CAGGTCGTTA EALKTYEKY ATCGAACAGG RADINKKINCTGAAAAACG AKDRAAIAA GCAGAAGGAT ALESVKLSDI GCGCAGAACG SSNLNRFSRCAGACAAGAA GLGYAGKFT GGCCGCTGAT SLADWITEF ATGCTTGCTG GKAVRTEN AATACGAGCGWRPLFVKTE CAGAAAAGGT TIIAGNAATA ATTCTGGACA LVALVFSILT CCCGGTTGTCGSALGIIGYG AGAGCTGGAA LLMAVTGAL AAAAATGGCG IDESLVEKA GGGCAGCCCT NKFWGITGCCGTTCTTG ATGCACAACA GGCCCGTCTG CTCGGGCAGC AGACACGGAA TGACAGGGCCATTTCAGAGG CCCGGAATAA ACTCAGTTCA GTGACGGAAT CGCTTAACAC GGCCCGTAATGCATTAACCA GAGCTGAACA ACAGCTGACG CAACAGAAAA ACACGCCTGA CGGCAAAACGATAGTTTCCCC TGAAAAATTC CCGGGGCGTT CATCAACAAA TGATTCTATTG TTGTGAGCGGTGATCCGAGA TTTGCCGGTA CGATAAAAAT CACAACCAGC GCAGTCATCG ATAACCGTGCAAACCTGAAT TATCTTCTGAG CCATTCCGGT CTGGACTATA AACGCAATAT TCTGAATGACCGGAATCCGG TGGTGACAGA GGATGTGGAA GGTGACAAGA AAATTTATAA TGCTGAAGTTGCTGAATGGG ATAAGTTACG GCAAAGATTG CTTGATGCCA GAAATAAAAT CACCTCTGCTGAATCTGCGG TAAATTCGGC GAGAAATAAC CTCAGTGCCA GAACAAATGA GCAAAAGCATGCAAATGACG CTCTTAATGCC CTGTTGAAGG AAAAAGAGAA TATCCGTAAC CAGCTTTCCGGCATCAATCA GAAGATAGCG GAAGAGAAAA GAAAACAGGA TGAACTGAAG GCAACGAAAGACGCAATTAA TTTCACAACA GAGTTCCTGA AATCAGTTTC AGAAAAATAT GGTGCAAAAGCTGAGCAGTT AGCCAGAGAG ATGGCCGGGC AGGCTAAAGG GAAGAAAATA CGTAATGTTGAAGAGGCATT AAAAACGTAT GAAAAGTACC GGGCTGACAT TAACAAAAAA ATTAATGCAAAAGATCGTGC AGCGATTGCC GCAGCCCTTG AGTCTGTGAA GCTGTCTGAT ATATCGTCTAATCTGAACAG ATTCAGTCGG GGACTGGGAT ATGCAGGAAA ATTTACAAGT CTTGCTGACTGGATCACTGA GTTTGGTAAG GCTGTCCGGA CAGAGAACTG GCGTCCTCTTT TTGTTAAAACAGAAACCATC ATAGCAGGCA ATGCCGCAAC GGCTCTTGTG GCACTGGTCT TCAGTATTCTTACCGGAAGCG CTTTAGGCATT ATCGGGTATG GTTTACTGAT GGCTGTCACC GGTGCGCTGATTGATGAATC GCTTGTGGAA AAAGCGAATA AGTTCTGGGG TATTTAA 58 Colicin-IbUnclassified MSDPVRITN Escherichia 59 ATGTCTGACC PGAESLGYD coliCTGTACGTATT SDGHEIMAV ACAAATCCCG DIYVNPPRV GTGCAGAATC DVFHGTPPAGCTGGGATAT WSSFGNKTI GATTCAGATG WGGNEWVD GCCATGAAAT DSPTRSDIEKTATGGCCGTT RDKEITAYK GATATTTATGT NTLSAQQKE AAACCCTCCA NENKRTEAGCGTGTCGATG KRLSAAIAA TCTTTCATGGT REKDENTLK ACCCCGCCTG TLRAGNADACATGGAGTTC ADITRQEFRL CTTCGGGAAC LQAELREYG AAAACCATCT FRTEIAGYDGGGGTGGAAA ALRLHTESR CGAGTGGGTC MLFADADSL GATGATTCCC RISPREARSLCAACCCGAAG IEQAEKRQK TGATATCGAA DAQNADKK AAAAGGGACA AADMLAEY AGGAAATCACERRKGILDT AGCGTACAAA RLSELEKNG AACACGCTCA GAALAVLDA GCGCGCAGCA QQARLLGQQGAAAGAGAAT TRNDRAISE GAGAATAAGC ARNKLSSVT GTACTGAAGC ESLKTARNATGGAAAACGC LTRAEQQLT CTTTCTGCGGC QQKNTPDGK AATTGCTGCA TIVSPEKFPGAGGGAAAAAG RSSTNHSIVV ATGAAAACAC SGDPRFAGTI ACTGAAAACA KITTSAVIDNCTCCGTGCCG RANLNYLLT GAAACGCAGA HSGLDYKRN TGCCGCTGAT ILNDRNPVVATTACACGAC TEDVEGDKK AGGAGTTCAG IYNAEVAEW ACTCCTGCAG DKLRQRLLDGCAGAGCTGA ARNKITSAES GAGAATACGG AINSARNNV ATTCCGTACT SARTNEQKHGAAATCGCCG ANDALNALL GATATGATGC KEKENIRSQ CCTCCGGCTG LADINQKIAECATACAGAGA EKRKRDEIN GCCGGATGCT MVKDAIKLT GTTTGCTGAT SDFYRTIYDEGCTGATTCTCT FGKQASELA TCGTATATCTC KELASVSQG CCCGCGAGGC KQIKSVDDACAGGTCGTTA LNAFDKFRN ATCGAACAGG NLNKKYNIQ CTGAAAAACG DRMAISKALGCAGAAGGAT EAINQVHMA GCGCAGAACG ENFKLFSKAF CAGACAAGAA GFTGKVIERGGCCGCTGAT YDVAVELQK ATGCTTGCTG AVKTDNWR AATACGAGCG PFFVKLESLACAGAAAAGGT AGRAASAVT ATTCTGGACA AWAFSVML CGCGGTTGTC GTPVGILGF AGAGCTGGAAAIIMAAVSA AAAAATGGCG LVNDKFIEQ GGGCAGCCCT VNKLIGI TGCCGTTCTTG ATGCACAACAGGCCCGTCTG CTCGGGCAGC AGACACGGAA TGACAGGGCC ATTTCAGAGG CCCGGAATAAACTCAGTTCG GTGACGGAAT CGCTTAAGAC GGCCCGTAAT GCATTAACCA GAGCTGAACAACAGCTGACG CAACAGAAAA ACACGCCTGA CGGCAAAACG ATAGTTTCCCC TGAAAAATTCCCGGGGCGTT CATCAACAAA TCATTCTATTG TTGTGAGTGG TGATCCGAGG TTTGCCGGTACGATAAAAAT CACAACCAGC GCGGTCATCG ATAACCGTGC AAACCTGAAT TATCTTCTGACCCATTCCGGT CTGGACTATA AACGCAATAT TCTGAATGAC CGGAATCCGG TGGTGACAGAGGATGTGGAA GGTGACAAGA AAATTTATAA TGCTGAAGTT GCTGAATGGG ATAAGTTACGGCAACGATTG CTTGATGCCA GAAATAAAAT CACCTCTGCT GAATCTGCGA TAAATTCGGCGAGAAATAAC GTCAGTGCCA GAACAAATGA ACAAAAGCAT GCAAATGACG CTCTTAATGCCCTGTTGAAGG AAAAAGAGAA TATCCGTAGC CAGCTTGCTG ACATCAATCA GAAAATAGCTGAAGAGAAAA GAAAAAGGGA TGAAATAAAT ATGGTAAAGG ATGCCATAAA ACTCACCTCTGATTTCTACAG AACGATATAT GATGAGTTCG GTAAACAAGC ATCCGAACTT GCTAAGGAGCTGGCTTCTGTA TCTCAAGGGA AACAGATTAA GAGTGTGGAT GATGCACTGA ACGCTTTTGATAAATTCCGTA ATAATCTGAA CAAGAAATAT AACATACAAG ATCGCATGGC CATTTCTAAAGCCCTGGAAG CTATTAATCA GGTCCATATG GCGGAGAATT TTAAGCTGTTC AGTAAGGCATTTGGTTTTACC GGAAAAGTTA TTGAACGTTA TGATGTTGCT GTGGAGTTAC AAAAGGCTGTAAAAACGGAC AACTGGCGTC CATTTTTTGTA AAACTTGAAT CACTGGCAGC AGGAAGAGCTGCTTCAGCAG TTACAGCATG GGCGTTTTCC GTCATGCTGG GAACCCCTGT AGGTATTCTGGGTTTTGCAA TTATTATGGC GGCTGTGAGT GCGCTTGTTA ATGATAAGTT TATTGAGCAGGTCAATAAAC TTATTGGTATC TGA 60 Colicin-M Unclassified METLTVHAPEscherichia 61 ATGGAAACCT SPSTNLPSYG coli TAACTGTTCAT NGAFSLSAPGCACCATCAC HVPGAGPLL CATCAACTAA VQVVYSFFQ CTTACCAAGTT SPNMCLQALATGGCAATGG TQLEDYIKK TGCATTTTCTC HGASNPLTL TTTCAGCACC QIISTNIGYFACATGTGCCT CNADRNLVL GGTGCTGGCC HPGISVYDA CTCTTTTAGTC YHFAKPAPSCAGGTTGTTT QYDYRSMN ATAGTTTTTTC MKQMSGNV CAGAGTCCAA TTPIVALAHACATGTGTCTT YLWGNGAE CAGGCTTTAA RSVNIANIGL CTCAACTTGA KISPMKINQIGGATTACATC KDIIKSGVV AAAAAACATG GTFPVSTKFT GGGCCAGCAA HATGDYNVICCCTCTCACAT TGAYLGNIT TGCAGATCAT LKTEGTLTIS ATCGACAAAT ANGSWTYNATTGGTTACTT GVVRSYDD CTGTAACGCC KYDFNASTH GACCGAAATC RGIIGESLTRTGGTTCTTCAC LGAMFSGKE CCTGGAATAA YQILLPGEIH GCGTTTATGA IKESGKRCGCTTACCACT TCGCAAAACC AGCGCCAAGT CAATATGACT ATCGCTCAAT GAATATGAAACAAATGAGCG GTAATGTCAC TACACCAATT GTGGCGCTTG CTCACTATTTA TGGGGTAATGGCGCTGAAAG GAGCGTTAAT ATCGCCAACA TTGGTCTTAA AATTTCCCCTA TGAAAATTAATCAGATAAAA GACATTATAA AATCTGGTGT AGTAGGCACA TTCCCTGTTTC TACAAAGTTCACACATGCCA CTGGTGATTA TAATGTTATTA CCGGTGCATA TCTTGGTAAT ATCACACTGAAAACAGAAGG TACTTTAACTA TCTCTGCCAAT GGCTCCTGGA CTTACAATGG CGTTGTTCGTTCATATGATGA TAAATACGAT TTTAACGCCA GCACTCACCG TGGCATTATC GGAGAGTCGCTCACAAGGCT CGGGGCGATG TTTTCTGGTAA AGAGTACCAG ATACTGCTTCC TGGTGAAATTCACATTAAAG AAAGTGGTAA GCGATAA 62 Colicin-N Unclassified MGSNGADNEscherichia 63 GCAAATCGAG AHNNAFGG coli TTTCGAATATA GKNPGIGNT AATAACATTASGAGSNGSA TATCTAGTGTT SSNRGNSNG ATTCGATGA WSWSNKPH KNDGFHSDG SYHITFHGDNNSKPKPGG NSGNRGNN GDGASAKV GEITITPDNS KPGRYISSNP EYSLLAKLID AESIKGTEVYTFHTRKGQ YVKVTVPDS NIDKMRVDY VNWKGPKY NNKLVKRFV SQFLLFRKEE KEKNEKEALLKASELVSG MGDKLGEY LGVKYKNV AKEVANDIK NFHGRNIRS YNEAMASLN KVLANPKMKVNKSDKD AIVNAWKQ VNAKDMAN KIGNLGKAF KVADLAIKV EKIREKSIEG YNTGNWGPLLLEVESWII GGVVAGVAI SLFGAVLSFL PISGLAVTAL GVIGIMTISY LSSFIDANRVSNINNIISSVIR 64 Colicin-V Unclassified MRTLTLNEL Escherichia 65ATGAGAACTC (Microcin- DSVSGGASG coli TGACTCTAAA V) RDIAMAIGT TGAATTAGATLSGQFVAGG TCTGTTTCTGG IGAAAGGVA TGGTGCTTCA GGAIYDYAS GGGCGTGATATHKPNPAMS TTGCGATGGC PSGLGGTIK TATAGGAACA QKPEGIPSEA CTATCCGGAC WNYAAGRLAATTTGTTGC CNWSPNNLS AGGAGGAATT DVCL GGAGCAGCTG CTGGGGGTGT GGCTGGAGGTGCAATATATG ACTATGCATC CACTCACAAA CCTAATCCTGC AATGTCTCCAT CCGGTTTAGGAGGAACAATT AAGCAAAAAC CCGAAGGGAT ACCTTCAGAA GCATGGAACT ATGCTGCGGGAAGATTGTGT AATTGGAGTC CAAATAATCT TAGTGATGTTT GTTTATAA 66 Columbicin ALantibiotic MMNATENQI Enterococcus 67 ATGATGAATG FVETVSDQE columbaeCTACTGAAAA LEMLIGGAG CCAAATTTTTG RGWIKTLTK TTGAGACTGT DCPNVISSICGAGTGACCAA AGTIITACKN GAATTAGAAA CA TGTTAATTGGT GGTGCAGGTC GTGGATGGATTAAGACTTTA ACAAAAGATT GTCCAAATGT GATTTCTTCAA TTTGTGCAGG TACAATTATTACAGCTTGTAA AAATTGTGCT TAA 68 Curvacin-A class MNNVKELS Lactobacillus 69ATGAATAATG IIA/YG MTELQTITG curvatus TAAAAGAATT NGV GARSYGNG AAGTATGACAVYCNNKKC GAATTACAAA WVNRGEAT CAATTACCGG QSIIGGMISG CGGTGCTAGA WASGLAGMTCATATGGCA ACGGTGTTTA CTGTAATAAT AAAAAATGTT GGGTAAATCG GGGTGAAGCAACGCAAAGTA TTATTGGTGG TATGATTAGC GGCTGGGCTA GTGGTTTAGC TGGAATGTAA 70Cypemycin Unclassified MRSEMTLTS Streptomyces 71 GTGCGATCTG TNSAEALAAsp. AGATGACTCT QDFANTVLS TACGAGCACG AAAPGFHAD AATTCCGCTG CETPAMATPAGGCTCTGGC ATPTVAQFV GGCGCAGGAC IQGSTICLVC TTTGCGAACA CCGTTCTCAGCGCGGCGGCC CCGGGCTTCC ACGCGGACTG CGAGACGCCG GCCATGGCCA CCCCGGCCACGCCGACCGTC GCCCAGTTCG TGATCCAGGG CAGCACGATC TGCCTGGTCT GCTGA 72Cytolysin Lantibiotic MVNSKDLR Bacillus 73 ATGGTAAATT NPEFRKAQGhalodurans CAAAAGATTT LQFVDEVNE (strain ATCC GCGTAATCCT KELSSLAGSBAA-125/ GAATTCCGCA GDVHAQTT DSM 18197/ AAGCCCAAGG WPCATVGVS FERM 7344/TCTACAATTCG VALCPTTKC JCM 9153/ TTGACGAGGT TSQC C-125) GAACGAGAAGGAACTTTCGT CTCTAGCTGG TTCAGGAGAT GTGCATGCAC AAACAACTTG GCCTTGCGCTACAGTTGGTG TCTCCGTAGC CTTGTGCCCA ACTACAAAGT GTACAAGCCA GTGCTAA 74Divercin class MKNLKEGSY Carnobacterium 75 ATGAAAAACT V41 IIa/YGNTAVNTDELK divergens TAAAAGAAGG GV SINGGTKYY (Lactobacillus TTCATACACTGGNGVYCNS divergens) CTGTTAATACT KKCWVDWG GATGAATTAA QASGCIGQT AAAGTATCAAVVGGWLGG TGGTGGAACA AIPGKC AAATATTATG GGAATGGCGT TTATTGCAATT CTAAAAAATGTTGGGTAGAT TGGGGACAAG CTTCAGGTTGT ATCGGTCAAA CTGTTGTTGG CGGATGGCTAGGCGGAGCTA TACCAGGTAA ATGCTAA 76 Divergicin Unclassified MIKREKNRTCarnobacterium 77 ATGATTAAAA 750 ISSLGYEEIS divergens GAGAAAAGAANHKLQEIQG (Lactobacillus CAGAACAATT GKGILGKLG divergens) TCTTCCCTTGGVVQAGVDF TTATGAAGAA VSGVWAGIK ATTTCTAATCA QSAKDHPNA TAAATTGCAAGAAATACAAG GTGGAAAAGG AATTCTTGGT AAACTAGGAG TAGTACAGGC AGGAGTGGATTTTGTATCAG GAGTGTGGGC TGGAATAAAA CAGTCTGCCA AAGATCATCC TAATGCGTAA 78Divergicin A Class IIc MKKQILKGL Carnobacterium 79 ATGAAAAAAC VIVVCLSGAdivergens AAATTTTAAA TFFSTPQQAS (Lactobacillus AGGGTTGGTT AAAPKITQKdivergens) ATAGTTGTTTG QKNCVNGQ TTTATCTGGG LGGMLAGA GCAACATTTTTLGGPGGVVL CTCAACACCA GGIGGAIAG CAACAAGCTT GCFN CTGCTGCTGC ACCGAAAATTACTCAAAAAC AAAAAAATTG TGTTAATGGA CAATTAGGTG GAATGCTTGC TGGAGCTTTGGGTGGACCTG GCGGAGTTGT GTTAGGTGGT ATAGGTGGTG CAATAGCAGG AGGTTGTTTTA ATTAA80 Durancin Q Unclassified MQTIKELNT Enterococcus 81 ATGCAAACGAMELQEIIGGE durans TCAAAGAATT NDHRMPYEL GAACACGATG NRPNNLSKG GAATTACAAGGAKCAAGIL AAATAATTGG GAGLGAVG AGGTGAAAAT GGPGGFISA GACCATCGGA GISAVLGCMTGCCTTACGA ATTGAACCGT CCAAATAATT TATCCAAAGG TGGGGCTAAG TGTGCTGCTGGAATACTTGG CGCTGGACTA GGCGCAGTAG GCGGTGGACC TGGCGGATTT ATTAGTGCCGGAATCAGTGC TGTTCTTGGTT GTATGTAA 82 Durancin Unclassified MQTIKELNTEnterococcus 83 ATGCAAACGA TW-49M MELQKIIGG durans TCAAAGAATT ENDHRMPYEGAACACGATG LNRPNNLSK GAATTACAAA GGAKCAAGI AAATAATTGG LGAGLGAVGAGGTGAAAAT GGPGGFISA GACCATCGGA GISAVLGCM TGCCTTACGA ATTGAACCGTCCAAATAATT TATCCAAAGG TGGAGCTAAG TGCGCTGCCG GAATACTTGG TGCTGGATTAGGCGCAGTAG GCGGTGGACC TGGCGGATTT ATTAGTGCCG GAATCAGTGC TGTTCTTGGTTGTATGTAA 84 Dysgalacticin Unclassified MKKLKRLVI Streptococcus 85ATGAAAAAAT SLVTSLLVIS dysgalactiae TAAAACGTCT STVPALVYA subsp.TGTTATCTCTC NETNNFAET equisimilis TTGTTACTTCA QKEITTNSEA (StreptococcusTTACTAGTAAT TLTNEDYTK equisimilis) TTCAAGTACA LTSEVKTIYT GTTCCAGCACNLIQYDQTK TTGTTTACGCT NKFYVDEDK AATGAAACAA TEQYYNYD ATAACTTTGC DESIKGVYLAGAAACTCAA MKDSLNDEL AAAGAAATTA NNNNSSNYS CAACAAATTC EIINQKISEIDAGAAGCAACA YVLQGNDIN TTAACCAATG NLIPSNTRVK AAGACTACAC RSADFSWIQTAAATTAACTT RCLEEAWGY CCGAAGTAAA AISLVTLKGI AACAATTTAT INLFKAGKFEACAAATCTGA AAAAKLASA TTCAATACGA TAGRIAGMA CCAAACAAAA ALFAFVATCAACAAATTTT GATTVS ACGTCGATGA AGACAAAACT GAACAATATT ATAACTACGA TGATGAAAGTATAAAAGGGG TTTATCTCATG AAAGATAGTT TGAACGATGA GTTAAACAAT AATAACTCTTCAAACTATTCT GAAATAATTA ATCAAAAAAT CTCTGAAATT GACTATGTCC TTCAAGGAAACGATATAAAT AATTTAATTCC TAGCAATACC AGAGTAAAAA GATCAGCAGA TTTTTCTTGGATTCAAAGATG TCTAGAAGAA GCATGGGGAT ATGCTATTAG TCTAGTTACTC TAAAAGGAATAATCAATCTA TTTAAAGCAG GAAAATTTGA AGCTGCTGCT GCTAAATTAG CTTCTGCTACAGCAGGTAGAA TCGCTGGAAT GGCTGCCTTA TTTGCTTTCGT AGCAACTTGC GGTGCGACAACTGTATCATAA 86 Enterocin Unclassified MKQYKVLN Enterococcus 87ATGAAGCAAT 1071A EKEMKKPIG faecalis ATAAAGTATT GESVFSKIGN (StreptococcusGAATGAAAAA AVGPAAYWI faecalis) GAAATGAAAA LKGLGNMSD AACCTATTGG VNQADRINRGGGAGAGTCG KKH GTTTTTAGTAA AATAGGTAAT GCTGTAGGTC CAGCTGCTTA TTGGATTTTAAAAGGATTAGG TAATATGAGT GATGTAAACC AAGCTGATAG AATTAATAGA AAGAAACATT AA 88Enterocin bacteriocins MGAIAKLVA Enterococcus 89 ATGGGAGCAA 7A withoutKFGWPIVKK faecalis TCGCAAAATT (Enterocin sequence YYKQIMQFI(Streptococcus AGTAGCAAAG L50A) leader GEGWAINKII faecalis) TTTGGATGGCDWIKKHI CAATTGTTAA AAAGTATTAC AAACAAATTA TGCAATTTATT GGAGAAGGATGGGCAATTAA CAAAATTATT GATTGGATCA AAAAACATAT TTAA 90 EnterocinUnclassified MGAIAKLVA Enterococcus 91 ATGGGAGCAA 7B KFGWPFIKK faecalisTCGCAAAATT FYKQIMQFIG (Streptococcus AGTAGCAAAG QGWTIDQIE faecalis)TTTGGATGGC KWLKRH CATTTATTAAA AAATTCTACA AACAAATTAT GCAGTTTATCGGACAAGGAT GGACAATAGA TCAAATTGAA AAATGGTTAA AAAGACATTGA 92 EnterocinClass II MLNKKLLEN Enterococcus 93 ATGTTAAATA 96 GVVNAVTID faecalisAAAAATTATT ELDAQFGGM (strain ATCC AGAAAATGGT SKRDCNLMK 700802/GTAGTAAATG ACCAGQAVT V583) CTGTAACAAT YAIHSLLNRL TGATGAACTT GGDSSDPAGGATGCTCAAT CNDIVRKYCK TTGGTGGAAT GAGCAAACGT GATTGTAACT TGATGAAGGCGTGTTGTGCT GGACAAGCAG TAACATATGC TATTCATAGTC TTTTAAATCGA TTAGGTGGAGACTCTAGTGA TCCAGCTGGT TGTAATGATA TTGTAAGAAA ATATTGTAAA TAA 94 EnterocinA Class MKHLKILSIK Enterococcus 95 ATGAAACATT IIa, IIc ETQLIYGGT faeciumTAAAAATTTT (problematic) THSGKYYGN (Streptococcus GTCTATTAAA GVYCTKNKCfaecium) GAGACACAAC TVDWAKAT TTATCTATGG TCIAGMSIG GGGTACCACT GFLGGAIPGCATAGTGGAA KC AATATTATGG AAATGGAGTG TATTGCACTA AAAATAAATG TACGGTCGATTGGGCCAAGG CAACTACTTGT ATTGCAGGAA TGTCTATAGG TGGTTTTTTAG GTGGAGCAATTCCAGGGAAG TGC 96 Enterocin Unclassified MVKENKFSK Enterococcus 97ATGGTTAAAG AS-48 IFILMALSFL faecalis AAAATAAATT (BACTERIOCINAS-GLALFSASL (Streptococcus TTCTAAGATTT 48) QFLPIAHMA faecalis) TTATTTTAATGKEFGIPAAV GCTTTGAGTTT AGTVLNVVE TTTGGGGTTA AGGWVTTIV GCCTTGTTTAGSILTAVGSG TGCAAGTCTT GLSLLAAAG CAGTTTTTGCC RESIKAYLK CATTGCACATKEIKKKGKR ATGGCTAAAG AVIAW AGTTCGGTAT ACCAGCAGCA GTTGCAGGAA CTGTGCTTAATGTAGTTGAAG CTGGTGGATG GGTCACTACT ATTGTATCAAT TCTTACTGCTG TAGGTAGCGGAGGTCTTTCTT TACTCGCTGC AGCAGGAAGA GAGTCAATTA AAGCATACCT TAAGAAAGAAATTAAGAAAA AAGGAAAAAG AGCAGTTATT GCTTGGTAA 98 Enterocin B class IIc,MQNVKELST Enterococcus 99 ATGCAAAATG non KEMKQIIGG faecium TAAAAGAATTsubgrouped ENDHRMPNE (Streptococcus AAGTACGAAA bacteriocins LNRPNNLSKfaecium) GAGATGAAAC (problematic) GGAKCGAAI AAATTATCGG AGGLFGIPKTGGAGAAAAT GPLAWAAGL GATCACAGAA ANVYSKCN TGCCTAATGA GTTAAATAGACCTAACAACT TATCTAAAGG TGGAGCAAAA TGTGGTGCTG CAATTGCTGG GGGATTATTTGGAATCCCAA AAGGACCACT AGCATGGGCT GCTGGGTTAG CAAATGTATA CTCTAAATGC AACTAA100 Enterocin Class IIa MKKLTSKE Enterococcus 101 TTGAAGAAAT CRL35MAQVVGGK mundtii TAACATCAAA (Mundticin YYGNGVSC AGAAATGGCA KS) NKKGCSVDCAAGTAGTAG WGKAIGIIGN GTGGAAAATA NSAANLATG CTACGGTAAT GAAGWKS GGAGTCTCATGTAATAAAAA AGGGTGCAGT GTTGATTGGG GAAAAGCTAT TGGCATTATT GGAAATAATTCTGCTGCGAA TTTAGCTACTG GTGGAGCAGC TGGTTGGAAA AGTTAA 102 EnterocinUnclassified MLAKIKAMI Enterococcus 103 ATGTTAGCAA EJ97 KKFPNPYTLfaecalis AAATTAAAGC AAKLTTYEI (Streptococcus GATGATTAAG NWYKQQYGfaecalis) AAGTTTCCGA RYPWERPVA ACCCTTATACT TTAGCAGCTA AGCTAACGACTTACGAAATT AATTGGTATA AACAACAATA CGGTCGTTAT CCTTGGGAGC GCCCTGTAGC ATAA104 Enterocin P Class MRKKLFSLA Enterococcus 105 ATGAGAAAAA IIa, IIbLIGIFGLVVT faecium AATTATTTAGT and IIc NFGTKVDAA (StreptococcusTTAGCTCTTAT (problematic) TRSYGNGVY faecium) TGGAATATTT CNNSKCWVGGGTTAGTTG NWGEAKENI TGACAAATTTT AGIVISGWA GGTACAAAAG SGLAGMGHTTGATGCAGC TACGCGTTCA TATGGTAATG GTGTTTATTGT AATAATAGTA AATGCTGGGTTAACTGGGGA GAAGCTAAAG AGAATATTGC AGGAATCGTT ATTAGTGGCT GGGCTTCTGGTTTGGCAGGT ATGGGACATT AA 106 Enterocin Q Class IIc MNFLKNGIAEnterococcus 107 ATGAATTTTCT KWMTGAEL faecium TAAAAATGGT QAYKKKYG(Streptococcus ATCGCAAAAT CLPWEKISC faecium) GGATGACCGG TGCTGAATTGCAAGCGTATA AAAAGAAATA TGGATGCTTG CCATGGGAAA AAATTTCTTGT TAA 108Enterocin Class IIa MKKKLVKG Enterococcus 109 ATGAAAAAGA SE-K4LVICGMIGIG faecalis AATTAGTTAA FTALGTNVE (Streptococcus AGGCTTAGTTAATYYGNG faecalis) ATTTGTGGCA VYCNKQKC TGATTGGGAT WVDWSRAR TGGTTTTACASEIIDRGVKA GCATTAGGAA YVNGFTKVL CAAATGTAGA GGIGGR AGCCGCCACG TATTACGGAAATGGTGTCTA TTGCAATAAG CAAAAATGTT GGGTAGATTG GAGTAGAGCA CGTTCTGAAATTATAGACAG AGGCGTAAAA GCATACGTCA ATGGATTTAC GAAAGTGTTA GGTGGTATAGGTGGAAGATAA 110 Enterocin Class IIb MKKEELVG Enterococcus 111 ATGAAAAAAGW alfa MAKEDFLNV faecalis AAGAATTAGT ICENDNKLE (Streptococcus AGGAATGGCTNSGAKCPW faecalis) AAGGAAGACT WNLSCHLGN TTTTAAATGTT DGKICTYSH ATTTGTGAAAECTAGCNA ATGACAACAA ACTAGAAAAT AGTGGAGCAA AATGTCCTTG GTGGAATCTTTCTTGTCATTT AGGCAATGAT GGTAAAATTT GCACTTATTCA CATGAATGTA CCGCAGGTTGTAATGCATAA 112 Enterocin Class IIb MTELNKRLQ Enterococcus 113 ATGACTGAACW beta LKRDVSTEN faecalis TTAACAAAAG SLKKISNTDE (StreptococcusATTACAATTA THGGVTTSIP faecalis) AAAAGAGATG CTVMVSAA TTTCAACAGA VCPTLVCSNAAATAGTTTG KCGGRG AAAAAAATTT CTAATACTGA TGAAACACAT GGGGGAGTTACTACATCAATT CCATGTACAG TAATGGTTAG TGCGGCAGTA TGTCCTACCCT TGTTTGCTCGAATAAATGTGG CGGTAGAGGC TAG 114 Enterocin Class IIb MQNVKEVS Enterococcus115 ATGCAAAATG Xalpha VKEMKQIIG faecium TAAAAGAAGT GSNDSLWY(Streptococcus TTCTGTAAAA GVGQFMGK faecium) GAGATGAAAC QANCITNHPAAATTATCGG VKHMIIPGY TGGTTCTAAT CLSKILG GATAGTCTTT GGTATGGTGT AGGACAATTTATGGGTAAAC AAGCAAACTG TATAACAAAC CATCCTGTTAA ACACATGATA ATTCCTGGATATTGTTTATCG AAAATTTTAG GGTAA 116 Enterocin Class IIb MKKYNELSKEnterococcus 117 ATGAAAAAAT Xbeta KELLQIQGGI faecium ATAATGAGTTAPIIVAGLGY (Streptococcus ATCTAAAAAA LVKDAWDH faecium) GAACTTCTACSDQIISGFKK AGATTCAAGG GWNGGRRK AGGAATAGCA CCTATTATAGT TGCTGGCCTTGGCTATTTAG TAAAAGATGC ATGGGATCAC TCAGATCAAA TAATCTCAGG ATTTAAAAAAGGTTGGAATG GTGGACGTAG AAAATAA 118 Enterolysin A class III MKNILLSILGEnterococcus 119 ATGAAAAATA VLSIVVSLAF faecalis TTTTACTTTCT SSYSVNAAS(Streptococcus ATTCTAGGGG NEWSWPLG faecalis) TATTATCTATC KPYAGRYEEGTTGTTTCTTT GQQFGNTAF GGCGTTTTCTT NRGGTYFHD CTTATTCTGTC GFDFGSAIYAACGCAGCTT GNGSVYAV CTAATGAGTG HDGKILYAG GTCGTGGCCA WDPVGGGS CTGGGCAAACLGAFIVLQA CATATGCGGG GNTNVIYQE AAGATATGAA FSRNVGDIK GAAGGACAAC VSTGQTVKKAATTCGGGAA GQLIGKFTSS CACTGCATTTA HLHLGMTK ACCGAGGAGG KEWRSAHSSTACTTATTTCC WNKDDGTW ATGATGGGTT FNPIPILQGG TGACTTTGGTT STPTPPNPGPCTGCTATTTAT KNFTTNVRY GGAAATGGCA GLRVLGGSW GTGTGTATGC LPEVTNFNNTGTGCATGAT TNDGFAGYP GGTAAAATTT NRQHDMLYI TATATGCTGG KVDKGQMK TTGGGATCCTYRVHTAQSG GTAGGTGGAG WLPWVSKG GCTCATTAGG DKSDTVNGA TGCATTTATTG AGMPGQAIDTACTACAAGC GVQLNYITP GGGAAACACA KGEKLSQAY AATGTGATTT YRSQTTKRSATCAAGAATT GWLKVSAD TAGCCGAAAT NGSIPGLDSY GTTGGAGATA AGIFGEPLDRTTAAAGTTAG LQIGISQSNPF CACTGGACAA ACTGTTAAAA AAGGACAGCT GATAGGAAAGTTTACTTCTAG TCATTTACATT TAGGAATGAC AAAAAAAGAA TGGCGTTCTG CTCATTCTTCTTGGAATAAAG ATGATGGCAC TTGGTTTAACC CAATTCCTATA CTTCAAGGAG GATCTACGCCTACGCCTCCA AATCCAGGAC CAAAAAATTT CACAACAAAT GTTCGTTACG GATTGCGGGTCCTCGGAGGT TCATGGTTAC CAGAAGTAAC CAACTTTAAC AATACCAATG ATGGTTTCGCAGGTTACCCT AATCGTCAAC ATGATATGCT TTATATAAAG GTAGATAAAG GGCAAATGAAATATCGTGTTC ACACGGCTCA AAGTGGATGG TTGCCTTGGG TAAGTAAAGG GGATAAGAGCGATACAGTAA ATGGAGCGGC AGGTATGCCT GGACAAGCAA TTGATGGTGT TCAGCTAAACTATATAACTCC TAAGGGAGAA AAATTATCAC AGGCTTACTA TCGTTCACAA ACTACGAAACGATCAGGCTG GTTAAAAGTA AGTGCAGATA ATGGTTCTATT CCTGGACTAG ACAGTTATGCAGGAATCTTT GGAGAACCGT TGGATCGCTT GCAAATAGGT ATTTCACAGTC AAATCCATTTT AA120 Epicidin Lantibiotic MENKKDLFD Staphylococcus 121 ATGGAAAACA 280LEIKKDNME epidermidis AAAAAGATTT NNNELEAQS ATTTGATTTAG LGPAIKATRAAATCAAAAA QVCPKATRF AGATAATATG VTVSCKKSD GAAAATAATA CQ ATGAATTAGAAGCTCAATCT CTTGGTCCTGC AATTAAGGCA ACTAGACAGG TATGTCCTAA AGCAACACGTTTTGTTACAGT TTCTTGTAAAA AAAGTGATTG TCAATAG 122 Epidermic UnclassifiedMAAFMKLIQ Staphylococcus 123 ATGGCAGCAT in NI01 FLATKGQKY epidermidisTTATGAAGTT VSLAWKHK AATTCAGTTCT GTILKWINA TAGCAACTAA GQSFEWIYKAGGTCAAAAG QIKKLWA TATGTTTCACT TGCATGGAAA CATAAAGGTA CTATTTTAAAATGGATTAACG CCGGTCAAAG TTTTGAATGG ATTTATAAAC AAATCAAAAA ATTATGGGCA TAA124 Epidermin Lantibiotic MEAVKEKN Staphylococcus 125 ATGGAAGCAGDLFNLDVKV epidermidis TAAAAGAAAA NAKESNDSG AAATGATCTTT AEPRIASKFITTAATCTTGAT CTPGCAKTG GTTAAAGTTA SFNSYCC ATGCAAAAGA ATCTAACGATTCAGGAGCTG AACCAAGAAT TGCTAGTAAA TTTATATGTAC TCCTGGATGT GCAAAAACAGGTAGTTTTAA CAGTTATTGTT GTTAA 126 Epilancin Lantibiotic MNNSLFDLNStaphylococcus 127 ATGAATAACT K7 LNKGVETQK epidermidis CATTATTCGATSDLSPQSAS TTAAACCTAA VLKTSIKVSK ACAAAGGTGT KYCKGVTLT AGAAACTCAACGCNITGGK AAGAGTGATT TAAGTCCGCA ATCTGCTAGT GTCTTGAAGA CTTCTATTAAAGTATCTAAAA AATATTGTAA AGGTGTTACT TTAACATGCG GTTGCAATAT TACTGGTGGT AAATAA128 Gallidermin Lantibiotic MEAVKEKN Staphylococcus 129 ATGGAAGCAGELFDLDVKV gallinarum TAAAAGAGAA NAKESNDSG AAATGAACTT AEPRIASKFLTTTGATCTTGA CTPGCAKTG CGTTAAAGTA SFNSYCC AATGCAAAAG AGTCTAATGATTCAGGCGCA GAACCACGAA TTGCTAGTAA ATTTTTATGTA CTCCTGGATG TGCCAAAACAGGTAGCTTCA ATAGCTACTG TTGTTAA 130 Garvicin A IId MENNNYTV Lactococcus131 ATGGAAAACA LSDEELQKID garvieae ACAATTACAC GGIGGALGN AGTACTTTCAALNGLGTW GATGAAGAAC ANMMNGGG TACAAAAAAT FVNQWQVY TGATGGTGGA ANKGKINQYATCGGCGGGG RPY CTCTTGGTAAT GCTCTCAACG GATTAGGTAC CTGGGCAAAC ATGATGAACGGTGGAGGATT TGTTAATCAG TGGCAAGTTT ATGCTAATAA AGGAAAAATA AATCAATACCGTCCGTATTAA 132 Garvicin Unclassified MFDLVATG Lactococcus 133ATGTTTGATTT ML MAAGVAKTI garvieae AGTCGCGACT VNAVSAGM GGAATGGCTGDIATALSLFS CAGGTGTAGC GAFTAAGGI AAAAACTATT MALIKKYAQ GTTAATGCCGKKLWKQLIAA TTAGTGCTGG TATGGATATT GCCACTGCTTT ATCATTGTTCT CAGGAGCTTTTACTGCAGCT GGGGGAATTA TGGCACTCAT TAAAAAATAT GCTCAAAAGA AATTATGGAAACAGCTTATT GCTGCATAA 134 Gassericin A Unclassified MVTKYGRNLactobacillus 135 ATGGTTACTA LGLNKVELF gasseri AGTACGGACG AIWAVLVVATAATTTAGGTT LLLTTANIY TGAACAAGGT WIADQFGIH AGAGTTGTTT LATGTARKLGCAATTTGGG LDAMASGAS CGGTTTTAGT LGTAFAAIL AGTTGCTCTTT GVTLPAWALTATTGACCAC AAAGALGAT AGCGAACATT AA TATTGGATTG CTGATCAATTC GGGATTCATTTAGCGACTGG AACAGCCCGT AAGTTATTAG ATGCAATGGC TTCTGGTGCCT CATTGGGAACTGCCTTTGCTG CTATTTTGGGC GTGACATTAC CTGCATGGGC TTTGGCAGCT GCAGGAGCATTGGGAGCGAC TGCAGCCTAG 136 Gassericin T Unclassified MKNFNTLSFLactobacillus 137 ATGAAAAATT (gassericin ETLANIVGG gasseri TTAATACATTAK7 B) RNNWAANIG TCATTTGAAA GVGGATVA CATTGGCTAA GWALGNAV CATAGTTGGTCGPACGFVG GGGAGAAATA AHYVPIAWA ATTGGGCTGC GVTAATGGF TAATATAGGT GKIRKGGAGTAGGTG GAGCGACAGT CGCTGGATGG GCTCTTGGAA ATGCAGTTTG CGGTCCTGCTTGTGGCTTTGTT GGAGCACACT ATGTTCCAAT AGCATGGGCT GGCGTAACGG CAGCTACTGGTGGATTCGGA AAGATAAGAA AGTAG 138 Glycocin F Unclassified MSKLVKTLTLactobacillus 139 ATGAGTAAAT ISEISKAQNN plantarum TGGTTAAGAC GGKPAWCWACTTACTATA YTLAMCGA AGTGAAATTT GYDSGTCDY CTAAGGCTCA MYSHCFGIK AAACAACGGTHHSSGSSSY GGAAAACCTG HC CATGGTGTTG GTATACTTTA GCAATGTGTG GTGCTGGTTATGATTCGGGA ACCTGTGATT ATATGTATTC GCATTGTTTTG GTATAAAGCA TCATAGTAGTGGTAGTAGCA GTTATCATTGT TAG 140 Halocin Unclassified MSKDRDGR Haloferax141 ATGTCGAAAG H4 RTSRRGTLK mediterranei ACAGAGATGG KIGGFSLGAL (strainATCC GAGAAGGACA SFGAVGRTQ 33500/DSM AGTCGGCGAG AATGSSVTT 1411/JCMGCACGTTAAA ADIAPPGPN 8866/ GAAAATCGGC GDPKSVQID NBRC 14739/ GGTTTCAGTCTDKYTGAEM NCIMB CGGAGCGCTT YGEGDFRVG 2177/R-4) AGTTTCGGGG LGTDLTMYP(Halobacterium CAGTCGGACG PVYRESLGN mediterranei) AACTCAAGCG GSGGWEFDFGCGACCGGCT TVCGSTACR CATCGGTTAC FVDSNGDVK GACCGCTGAT EDDKAKEM ATCGCACCTCWWQEINFND CCGGACCGAA INQDLYSRN CGGAGACCCG DSDWVGSTP AAGAGTGTTC ADTQPEFDYAGATAGATGA TEFALARDG TAAATACACC VTLALTALN GGAGCCGAGA PAMGSLALGTGTACGGCGA ATYFLSDMV GGGTGACTTC NWIASQHED AGAGTCGGTC DSSLKRKWDTCGGAACTGA YDGLSGPLY CCTGACGATG ADSSTYLLA TATCCGCCCG RDEMTSNSYTGTACCGTGA ESFTIDNIAV GAGTCTTGGA AFPEFPVRTK AATGGAAGCG YYVTFTAPDGGGGTTGGGA DPSTQSISTL ATTCGACTTCA EEEGIYRVP CCGTTTGTGG ATEVAAARPGTCCACTGCC PGSRRSKSA TGTCGATTTGT ADEMVYVA GGACAGTAAC DPKKFIEVEPGGTGACGTCA VKNPSIPDRI AAGAGGACGA YEEIEQKKK CAAGGCGAAA QRSRKQ GAAATGTGGTGGCAGGAAAT TAACTTCAAC GACATAAATC AGGATTTATA CAGTCGGAAC GATTCCGACTGGGTCGGGTC GACCCCTGCC GATACCCAAC CGGAGTTCGA TTACACCGAC TTTGCGCTCGCTCGGGACGGA GTGACGCTCG CTCTCACGGC ACTCAACCCC GCAATGGGGA GTCTTGCACTCGGTGCCACGT ACTTCCTCAGC GACATGGTGA ACTGGATTGC GAGCCAGCAC GAAGACGACAGTTCGCTCAA GAGAAAATGG GATTACGACG GGCTAAGTGG GCCGTTGTAC GCCGATTCGTCGACGTACCT ACTGGCACGC GACGAGATGA CTTCGAACTC GTACGAATCA TTCACGATCGATAACATCGC CGTTGCCTTCC CAGAGTTCCC CGTCCGGACC AAGTACTACG TCACATTCACTGCGCCGGATG ACCCGTCAAC GCAGTCGATA TCTACGCTCG AAGAGGAGGG AATCTACCGAGTGCCCGCTA CGGAAGTGGC TGCGGCCAGA CCACCGGGGT CCCGACGTTC CAAATCGGCAGCCGACGAGA TGGTGTACGT TGCCGATCCG AAGAAGTTCA TAGAGGTCGA GCCGGTGAAGAACCCAAGTA TCCCGGACCG AATCTACGAG GAGATAGAGC AAAAAAAGAA ACAACGGAGTAGGAAACAGT AG 142 Halocin- Unclassified MSDKDSINR Haloarchaeon 143ATGTCGGATA S8 RNVLRKIGGI S8a AAGACAGCAT GVASAVGFS TAACAGAAGA GLASGESLSAATGTATTAA DDEKQDVID GAAAAATTGG TIYKSQRVE CGGTATCGGT QIKKKFGGVGTGGCTTCAG NIEPKKVQS CTGTCGGATTT VTTNQSGDL TCTGGTTTGG VTAKLSVSDCAAGCGGGGA GDLVYSSVK AAGTCTTAGC DTTVIVQFD GATGATGAGA RSASEIGESAACAAGATGT WPKNTEAFI TATTGACACA KSTSSGVDL ATTTACAAAT LRTATDEEIKCACAAAGAGT DVTEGVNTS TGAACAGATA EIESADAVNI AAGAAAAAGT FIDPESQTYYTCGGAGGAGT MEKYDFNN GAATATTGAG KVLEMFELA CCGAAAAAGG TGGTSSGKISTTCAATCTGTA PTREDQNHE ACGACCAATC YNVREHKVF AGAGCGGAGA NSEKQNIQLTCTTGTTACGG QSDCNINSN CGAAGCTGTC TAADVILCF GGTTAGTGAT NQVGSCALCGGGGATTTGG SPTLVGGPV TATATTCGAG PTVACLLVV TGTCAAAGAT CFGTPNAVSACAACTGTAA AILEEVDNS TAGTTCAGTTC CFNLIKDVIS GATAGATCGG CWDEWTSFWCTTCTGAAATT GGTGAAAGTT GGCCCAAGAA TACTGAGGCA TTCATCAAATC GACGTCCTCTGGGGTCGATC TTCTACGTACA GCAACTGATG AAGAAATAAA GGACGTTACT GAGGGAGTCAACACATCTGA AATTGAATCT GCGGATGCTG TTAACATATTT ATTGATCCTG AATCACAGACATACTATATG GAGAAATATG ACTTTAATAAT AAGGTACTTG AGATGTTTGA ATTAGCGACAGGTGGGACAA GTAGTGGTAA AATCTCCCCC ACACGTGAAG ACCAGAATCA CGAATATAATGTTAGGGAAC ATAAAGTATT TAACTCAGAA AAACAGAATA TACAACTTCA GAGTGACTGTAATATAAACA GTAACACCGC TGCTGATGTT ATTCTATGCTT CAACCAGGTT GGTTCTTGTGCACTCTGCTCC CCGACTTTAG TCGGAGGTCC AGTCCCTACA GTTGCATGTCT CTTAGTCGTCTGTTTCGGCAC TCCAAATGCT GTGTCCGCGA TACTTGAAGA AGTCGATAAT TCTTGCTTTAACTTGATCAAG GATGTAATTT CGTGTTGGGA TGAATGGACT AGCTTCTGGT GA 144Helveticin-J Unclassified MKHLNETTN Lactobacillus 145 ATGAAGCATTVRILSQFDM helveticus TAAATGAAAC DTGYQAVV (Lactobacillus AACTAATGTTQKGNVGSK suntoryeus) AGAATTTTAA YVYGLQLRK GTCAATTTGA GATTILRGYTATGGATACT RGSKINNPIL GGCTATCAAG ELSGQAGGH CAGTAGTTCA TQTWEFAGDAAAAGGCAAT RKDINGEER GTAGGTTCAA AGQWFIGVK AATATGTATA PSKIEGSKIITGGATTACAA WAKQIARVD CTTCGCAAAG LRNQMGPH GTGCTACTAC YSNTDFPRLTATCTTGCGTG SYLNRAGSN GTTACCGTGG PFAGNKMTH AAGTAAAATT AEAAVSPDYAATAACCCTA TKFLIATVEN TTCTTGAATTA NCIGHFTIYN TCTGGTCAAG LDTINEKLDCAGGTGGTCA EKGNSEDVN CACACAGACA LETVKYEDS TGGGAATTTG FIIDNLYGDDCTGGTGATCG NNSIVNSIQG TAAAGACATT YDLDNDGNI AATGGTGAAG YISSQKAPDFAAAGAGCAGG DGSYYAHH TCAATGGTTT KQIVKIPYYA ATAGGTGTTA RSKESEDQWAACCATCGAA RAVNLSEFG AATTGAAGGA GLDIPGKHS AGCAAAATTA EVESIQIIGETTTGGGCAAA NHCYLTVAY GCAAATTGCA HSKNKAGEN AGAGTTGATC KTTLNEIYELTTAGAAATCA SWN AATGGGACCT CATTATTCAA ATACTGACTTT CCTCGATTATC CTACTTGAATCGCGCCGGTTC TAATCCATTTG CTGGTAATAA GATGACGCAT GCCGAAGCCG CAGTATCACCTGATTATACTA AGTTTTTAATT GCTACTGTTG AAAATAACTG TATTGGTCATT TTACTATATACAATTTAGATA CAATTAATGA AAAACTTGAT GAAAAGGGAA ATAGTGAAGA TGTTAATCTCGAAACTGTTAA ATACGAAGAT AGTTTTATCAT TGATAATTTAT ATGGTGATGA TAATAATTCTATTGTAAATTCA ATTCAAGGGT ATGATTTGGA TAATGATGGA AATATTTATAT TTCCAGTCAAAAAGCGCCAG ATTTTGATGG CTCTTATTATG CACATCATAA GCAGATTGTT AAGATTCCATATTATGCTCG GTCTAAAGAA AGCGAAGACC AATGGAGAGC TGTAAATTTA AGCGAATTCGGTGGCTTGGA TATTCCAGGT AAACATAGTG AAGTTGAAAG CATCCAAATT ATTGGTGAGAATCATTGTTAC TTAACTGTTGC ATATCATTCTA AAAATAAAGC GGGTGAAAAT AAAACTACTTTGAATGAGAT TTATGAATTAT CTTGGAATTAG 146 Hiracin Class II MKKKVLKHEnterococcus 147 ATGAAAAAGA JM79 sec- CVILGILGTC hirae AAGTATTAAAdependent LAGIGTGIKV ACATTGTGTT DAATYYGN ATTCTAGGAA GLYCNKEKC TATTAGGAACWVDWNQAK TTGTCTAGCTG GEIGKIIVNG GCATCGGTAC WVNHGPWA AGGAATAAAA PRRGTTGATGCAG CTACTTACTAT GGAAATGGTC TTTATTGTAAC AAAGAAAAAT GTTGGGTAGATTGGAATCAA GCTAAAGGAG AAATTGGAAA AATTATTGTTA ATGGTTGGGT TAATCATGGTCCATGGGCAC CTAGAAGGTAG 148 Lactacin- class IIB MKQFNYLSH Lactobacillus149 ATGAAACAAT F (lafA) KDLAVVVG johnsonii TTAATTATTTA GRNNWQTN (strainTCACATAAAG VGGAVGSA CNCM I- ATTTAGCAGT MIGATVGGT 12250/Lal/ CGTTGTTGGTICGPACAVA NCC 533) GGAAGAAATA GAHYLPILW ATTGGCAAAC TAVTAATGG AAATGTGGGAFGKIRK GGAGCAGTGG GATCAGCTAT GATTGGGGCT ACAGTTGGTG GTACAATTTG TGGACCTGCATGTGCTGTAG CTGGTGCCCA TTATCTTCCTA TTTTATGGAC AGCGGTTACA GCTGCAACAGGTGGTTTTGG CAAGATAAGA AAGTAG 150 Lactacin- class IIB MKLNDKELSLactobacillus 151 ATGAAATTAA F (lafX) KIVGGNRWG johnsonii ATGACAAAGADTVLSAASG (strain ATTATCAAAG AGTGIKACK NCM I- ATTGTTGGTG SFGPWGMAI12250/Lal/ GAAATCGATG CGVGGAAIG NCC 533) GGGAGATACT GYFGYTHN GTTTTATCAGCTGCTAGTGGC GCAGGAACTG GTATTAAAGC ATGTAAAAGT TTTGGCCCAT GGGGAATGGCAATTTGTGGT GTAGGAGGTG CAGCAATAGG AGGTTATTTTG GCTATACTCAT AATTAA 152Lacticin Lantibiotic MNKNEIETQ Lactococcus 153 ATGAACAAAA 3147 A1PVTWLEEVS lactis subsp. ATGAAATTGA DQNFDEDVF lactis AACACAACCA GACSTNTFS(Streptococcus GTTACATGGT LSDYWGNN lactis) TGGAAGAAGT GAWCTLTHEATCTGATCAA CMAWCK AATTTTGATG AAGATGTATT TGGTGCGTGT AGTACTAACACATTCTCGCTC AGTGATTACT GGGGAAATAA CGGGGCTTGG TGTACACTCA CTCATGAATGTATGGCTTGG TGTAAATAA 154 Lacticin Lantibiotic MKEKNMKK Lactococcus 155ATGAAAGAAA 3147 A2 NDTIELQLG lactis subsp. AAAATATGAA KYLEDDMIE lactisAAAGAATGAC LAEGDESHG (Streptococcus ACTATTGAATT GTTPATPAIS lactis)ACAATTGGGA ILSAYISTNT AAATACCTTG CPTTKCTRAC AAGATGATAT GATTGAATTAGCTGAAGGGG ATGAGTCTCA TGGAGGAACA ACACCAGCAA CTCCTGCAATC TCTATTCTCAGTGCATATATTA GTACCAATAC TTGTCCAACA ACAAAATGTA CACGTGCTTG TTAA 156Lacticin Lantibiotic MKEQNSFNL Lactococcus 157 ATGAAAGAAC 481 LQEVTESELlactis subsp. AAAACTCTTTT (Lactococcin DLILGAKGG lactis AATCTTCTTCA DR)SGVIHTISHE (Streptococcus AGAAGTGACA CNIVINSWQF lactis) GAAAGTGAATVFTCCS TGGACCTTATT TTAGGTGCAA AAGGCGGCAG TGGAGTTATT CATACAATTTCTCATGAATGT AATATGAATA GCTGGCAATT TGTATTTACTT GCTGCTCTTAA 158 Lacticin QUnclassified MAGFLKVV Lactococcus 159 ATGGCAGGGT QLLAKYGSK lactisTTTTAAAAGT AVQWAWAN AGTTCAATTA KGKILDWLN CTAGCTAAAT AGQAIDWV ATGGTTCTAAVSKIKQILGIK AGCTGTACAA TGGGCTTGGG CAAACAAGGG TAAGATTTTA GATTGGCTTAATGCAGGTCA GGCTATTGAT TGGGTAGTTT CGAAAATTAA GCAAATTTTA GGTATTAAGT AA 160Lacticin Z Unclassified MAGFLKVV Lactococcus 161 ATGGCAGGGT QILAKYGSKlactis TTTTAAAAGT AVQWAWAN AGTCCAAATT KGKILDWIN TTGGCTAAGT AGQAIDWVATGGTTCTAA VEKIKQILGIK AGCCGTACAA TGGGCATGGG CAAATAAAGG AAAAATCTTAGATTGGATTA ATGCAGGTCA AGCTATTGAC TGGGTAGTTG AAAAGATTAA GCAAATTTTGGGTATTAAAT AA 162 Lactobin-A class IIB MKQLNSEQL Lactobacillus 163ATGAAACAAT (Amylovorin- QNIIGGNRW amylovorus TGAATTCAGA L471) TNAYSAALGACAATTACAA CAVPGVKYG AATATTATCG KKLGGVWG GTGGAAATAG AVIGGVGGA ATGGACTAATAVCGLAGY GCATACAGCG VRKG CAGCTTTGGG ATGCGCTGTC CCTGGAGTTA AATATGGAAAAAAACTTGGT GGCGTATGGG GTGCTGTAAT TGGTGGCGTA GGCGGTGCAG CAGTCTGTGGCTTGGCGGGT TATGTTCGTA AAGGCTAA 164 Lactocin-S Lantibiotic MKTEKKVLLactobacillus 165 ATGAAAACAG DELSLHASA sakei L45 AAAAAAAGGT KMGARDVETTTAGATGAA SSMNADSTP CTGAGCTTAC VLASVAVSM ACGCTTCTGC ELLPTASVLAAAAATGGGA YSDVAGCFK GCACGTGATG YSAKHHC TTGAATCCAG CATGAATGCA GACTCAACACCAGTTTTAGC ATCAGTCGCT GTATCCATGG AATTATTGCC AACTGCGTCT GTTCTTTATTCGGATGTTGCA GGTTGCTTCA AATATTCTGC AAAACATCAT TGTTAG 166 LactococcinUnclassified MKTKSLVLA Lactococcus 167 ATGAAAACCA 972 LSAVTLFSA lactissubsp. AGTCTCTCGT GGIVAQAEG lactis ATTGGCATTA TWQHGYGV (StreptococcusTCTGCGGTTA SSAYSNYHH lactis) CGTTATTCTCT GSKTHSATV GCCGGAGGAA VNNNTGRQTTGTAGCTCA GKDTQRAG AGCTGAAGGA VWAKATVG ACATGGCAAC RNLTEKASF ATGGATATGGYYNFW TGTTAGTTCG GCATATTCAA ATTATCATCAT GGTAGCAAAA CTCATTCAGCCACAGTTGTAA ATAATAATAC TGGCCGACAA GGTAAGGATA CACAACGTGC CGGTGTTTGGGCAAAAGCTA CTGTTGGACG TAACTTAACT GAAAAAGCTT CATTTTATTAT AACTTTTGGT AA168 Lactococcin-A Unclassified MKNQLNFNI Lactococcus 169 ATGAAAAATCVSDEELSEA lactis subsp. AATTAAATTTT NGGKLTFIQ cremoris AATATTGTTTCSTAAGDLYY (Streptococcus AGATGAAGAA NTNTHKYV cremoris) CTTTCAGAAGYQQTQNAFG CTAACGGAGG AAANTIVNG AAAATTAACA WMGGAAGG TTTATTCAATC FGLHHGACAGCGGCT GGAGATTTAT ATTACAATAC TAATACACAC AAATATGTTT ACCAACAAACTCAAAACGCT TTTGGGGCTG CTGCTAATAC CATTGTTAAT GGATGGATGG GTGGCGCTGCTGGAGGTTTC GGGTTGCACC ATTGA 170 Lactococcin-B Unclassified MKNQLNFNILactococcus 171 ATGAAAAATC VSDEELAEV lactis subsp. AATTAAATTTT NGGSLQYVcremoris AATATTGTTTC MSAGPYTW (Streptococcus TGATGAAGAA YKDTRTGKTcremoris) CTTGCAGAAG ICKQTIDTAS TTAATGGAGG YTFGVMAE AAGCTTGCAG GWGKTFHTATGTTATGA GTGCTGGACC ATATACTTGG TATAAAGATA CTAGAACAGG AAAAACAATATGTAAACAGA CAATTGACAC AGCAAGTTAT ACATTTGGTG TAATGGCAGA AGGATGGGGAAAAACATTCC ACTAA 172 Lactocyclicin Q Unclassified MKLIDHLGA Lactococcus173 ATGAAATTAA PRWAVDTIL sp. QU 12 TTGATCATTTA GAIAVGNLA GGTGCTCCAASWVLALVPG GATGGGCCGT PGWAVKAG TGATACTATTT LATAAAIVK TAGGTGCAAT HQGKAAAACGCAGTTGGG AW AACTTAGCAA GTTGGGTTCT AGCGCTTGTC CCTGGTCCAG GGTGGGCAGTAAAAGCTGGT TTAGCAACTG CTGCTGCCAT CGTTAAACAT CAAGGTAAAG CTGCCGCTGCTGCTTGGTAA 174 Laterosporulin Unclassified MACQCPDAI Brevibacillus 175ATGGCTTGCC SGWTHTDY sp. GI-9 AATGTCCAGA QCHGLENK TGCGATCTCA MYRHVYAICGGTTGGACGC MNGTQVYC ATACAGATTA RTEWGSSC CCAGTGTCAC GGTTTGGAGA ATAAAATGTATAGACATGTT TATGCAATTT GCATGAACGG TACTCAAGTA TATTGCAGAA CAGAGTGGGGTAGCAGCTGC TAG 176 Leucocin N Class IId MNKEYNSIS Leuconostoc 177ATGAATAAAG NFKKITNKD pseudomesenteroides AATATAATAG LQNINGGFIGCATTAGCAAT RAIGDFVYF TTTAAAAAAA GAKGLRESG TTACTAATAA KLLNYYYKHAGACTTGCAA KH AACATAAATG GTGGATTTATT GGTAGGGCAA TAGGTGACTT TGTGTACTTTGGAGCGAAGGG ACTAAGAGAA TCTGGTAAAC TACTTAATTAT TACTATAAGC ATAAGCATTGA 178Leucocin Q Class IId MKNQLMSFE Leuconostoc 179 ATGAAAAATC VISEKELSTVpseudomesenteroides AGTTAATGTC QGGKGLGKL TTTCGAAGTG IGIDWLLGQ ATATCAGAAAAKDAVKQY AAGAATTGTC KKDYKRWH CACGGTACAA GGTGGCAAAG GCTTAGGTAA ACTCATAGGAATTGATTGGC TTTTGGGTCA AGCTAAGGAC GCTGTTAAAC AGTACAAGAA GGATTACAAACGTTGGCACT AA 180 Leucocin-A class MMNMKPTE Leuconostoc 181 ATGATGAACA(Leucocin IIA/YG SYEQLDNSA gelidum TGAAACCTAC A-UAL NGV LEQVVGGKGGAAAGCTAT 187) YYGNGVHC GAGCAATTGG TKSGCSVNW ATAATAGTGC GEAFSAGVHTCTCGAACAA RLANGGNGFW GTCGTAGGAG GTAAGTATTA TGGTAACGGA GTTCATTGCACAAAAAGTGG TTGTTCTGTAA ACTGGGGAGA AGCCTTTTCA GCTGGAGTAC ATCGTTTAGCAAATGGTGGA AATGGTTTCT GGTAA 182 Leucocin-B class MNNMKSAD Leuconostoc183 ATGAATAACA (Leucocin IIA/YG NYQQLDNN carnosum TGAAATCTGC B-Ta11a)NGV ALEQVVGGK GGATAATTAT YYGNGVHC CAGCAATTGG TKSGCSVNW ATAATAATGCGEAFSAGVH TCTCGAACAA RLANGGNGFW GTCGTAGGAG GTAAGTATTA TGGTAACGGAGTTCATTGCA CAAAAAGTGG TTGTTCTGTAA ACTGGGGAGA AGCCTTTTCA GCTGGAGTACATCGTTTAGC AAATGGTGGA AATGGTTTCT GGTAA 184 Leucocyclicin Q UnclassifledMFLVNQLGI Leuconostoc 185 ATGTTCTTGGT SKSLANTILG mesenteroidesAAATCAGTTA AIAVGNLAS GGGATTTCAA WLLALVPGP AATCGTTAGC GWATKAALTAATACTATTC ATAETIVKH TTGGTGCAAT EGKAAAIAW TGCTGTTGGT AATTTGGCCAGTTGGTTATTA GCTTTGGTTCC TGGTCCGGGT TGGGCAACAA AAGCAGCACT TGCGACAGCTGAAACAATTG TGAAGCATGA AGGAAAAGCA GCTGCTATTG CGTGGTAA 186 LichenicidinLantibiotic MSKKEMILS Bacillus 187 ATGTCAAAAA A1 (two- WKNPMYRTlicheniformis AGGAAATGAT peptide) ESSYHPAGNI (strain DSM TCTTTCATGGALKELQEEEQ 13/ATCC AAAATCCTAT HSIAGGTITL 14580) GTATCGCACT STCAILSKPLGAATCTTCTTA GNNGYLCTV TCATCCAGCA TKECMPSCN GGGAACATCC TTAAAGAACTCCAGGAAGAG GAACAGCACA GCATCGCCGG AGGCACAATC ACGCTCAGCA CTTGTGCCATCTTGAGCAAGC CGTTAGGAAA TAACGGATAC CTGTGTACAG TGACAAAAGA ATGCATGCCAAGCTGTAACT AA 188 Linocin Unclassified MNNLYRELA Brevibacterium 189GTGAATAACC M18 PIPGPAWAEI linens TCTATCGCGA EEEARRTFK GCTTGCCCCCRNIAGRRIV ATCCCCGGCC DVAGPTGFE CGGCCTGGGC TSAVTTGHI GGAGATCGAG RDVQSETSGGAGGAGGCTC LQVKQRIVQ GACGGACATT EYIELRTPFT CAAACGCAAT VTRQAIDDVATCGCCGGCC ARGSGDSD GCCGGATCGT WQPVKDAA CGATGTCGCA TTIAMAEDR GGGCCCACGGAILHGLDAA GCTTCGAGAC GIGGIVPGSS CTCCGCGGTG NAAVAIPDA ACCACTGGCCVEDFADAVA ACATCCGAGA QALSVLRTV CGTCCAGTCG GVDGPYSLL GAGACGAGCG LSSAEYTKVGACTGCAGGT SESTDHGYPI TAAGCAGCGC REHLSRQLG ATCGTGCAGG AGEIIWAPALAATACATCGA EGALLVSTR GCTGCGGACC GGDYELHLG CCATTCACCGT QDLSIGYYSGACTCGGCAG HDSETVELY GCCATCGATG LQETFGFLA ACGTGGCCCG LTDESSVPLSLCGGGTCCGGT GACTCGGACT GGCAGCCCGT CAAGGATGCG GCCACGACGA TCGCGATGGCTGAAGATCGG GCCATTCTCCA CGGGCTCGAT GCGGCCGGGA TCGGCGGAAT CGTTCCCGGCAGCTCGAATG CCGCAGTGGC CATCCCCGAC GCCGTCGAGG ACTTCGCGGA CGCCGTCGCCCAGGCGCTGA GTGTGCTGCG CACGGTGGGA GTCGACGGGC CCTACAGCCT GTTGCTCTCCTCCGCGGAGTA CACCAAGGTC TCCGAGTCCA CCGACCACGG CTACCCGATC CGCGAGCACCTCTCCCGGCA GCTCGGCGCC GGAGAGATCA TCTGGGCGCC CGCGCTCGAA GGGGCGCTGCTCGTCTCCAC GCGCGGGGGT GACTACGAGC TCCACCTCGG CCAGGACCTG TCGATCGGTTACTACAGCCA CGACAGCGAG ACCGTCGAAC TCTATCTGCA GGAGACCTTC GGATTCCTCGCGCTGACCGA CGAATCCAGT GTGCCTTTGA GCCTCTGA 190 Listeriocin Class IIaMKKAALKFII Listeria 191 TTGAAGAAGG 743A VIAILGFSFSF innocua CAGCGTTAAAFSIQSEAKSY ATTTATTATTG GNGVQCNK TTATTGCTATT KKCWVDWG CTAGGTTTCASAISTIGNNS GTTTTTCTTTC AANWATGG TTTAGCATAC AAGWKS AATCTGAAGC TAAATCTTATGGAAATGGAGT TCAGTGTAAT AAGAAAAAAT GTTGGGTAGA TTGGGGTAGT GCTATAAGTACTATTGGAAA TAATTCTGCA GCGAATTGGG CTACAGGTGG AGCAGCTGGT TGGAAAAGCT GA 192Mersacidin Lantibiotic, MSQEAIIRS Bacillus sp. 193 ATGAGTCAAG type BWKDPFSREN (strain HIL- AAGCTATCAT STQNPAGNP Y85/54728) TCGTTCATGGFSELKEAQM AAAGATCCTT DKLVGAGD TTTCCCGTGA MEAACTFTL AAATTCTACA PGGGGVCTLCAAAATCCAG TSECIC CTGGTAACCC ATTCAGTGAG CTGAAAGAAG CACAAATGGA TAAGTTAGTAGGTGCGGGAG ACATGGAAGC AGCATGTACT TTTACATTGCC TGGTGGCGGC GGTGTTTGTACTCTAACTTCT GAATGTATTT GTTAA 194 Mesentericin class MTNMKSVE Leuconostoc195 ATGACGAATA Y105 IIA/YG AYQQLDNQ mesenteroides TGAAGTCTGT NGVNLKKVVGG GGAAGCATAT KYYGNGVH CAGCAATTAG CTKSGCSVN ATAACCAGAA WGEAASAGITCTCAAGAAA HRLANGGN GTTGTTGGTG GFW GAAAGTATTA TGGGAATGGT GTTCACTGTACAAAAAGTGG ATGCTCTGTTA ACTGGGGAGA AGCTGCCTCA GCTGGCATAC ATCGTTTGGCCAATGGTGGA AATGGATTTT GGTAA 196 Michiganin-A Lantibiotic MNDILETETClavibacter 197 ATGAACGACA PVMVSPRW michiganensis TCCTCGAGAC DMLLDAGEsubsp. GGAGACCCCC DTSPSVQTQI michiganensis GTCATGGTCA DAEFRRVVSGCCCCCGGTG PYMSSSGWL GGACATGCTG CTLTIECGTII CTCGACGCGG CACR GCGAGGACACCAGCCCGTCC GTCCAGACCC AGATCGACGC GGAGTTCCGT CGCGTCGTGA GCCCGTACATGTCCAGCAGC GGCTGGCTCT GCACGCTCAC CATCGAATGT GGCACCATCA TCTGCGCGTGTCGCTGA 198 Microcin Unclassified MELKASEFG Escherichia 199 ATGGAATTAAB17 VVLSVDALK coli AAGCGAGTGA (MccB17) LSRQSPLGV ATTTGGTGTA GIGGGGGGGGTTTTGTCCGT GGGSCGGQ TGATGCTCTTA GGGCGGCSN AATTATCACG GCSGGNGGSCCAGTCTCCAT GGSGSHI TAGGTGTTGG CATTGGTGGT GGTGGCGGCG GCGGCGGCGGCGGTAGCTGC GGTGGTCAAG GTGGCGGTTG TGGTGGTTGC AGCAACGGTT GTAGTGGTGGAAACGGTGGC AGCGGCGGAA GTGGTTCACA TATC 200 Microcin Unclassified MRTGNANEscherichia 201 ATGCGTACTG C7 coli GTAATGCAAA CTAA 202 MicrocinUnclassified MREISQKDL Klebsiella 203 ATGAGAGAAA E492 NLAFGAGETpneumoniae TTAGTCAAAA DPNTQLLND GGACTTAAAT LGNNMAWG CTTGCTTTTGGAALGAPGGL TGCAGGAGAG GSAALGAAG ACCGATCCAA GALQTVGQ ATACTCAACTT GLIDHGPVNCTAAACGACC VPIPVLIGPS TTGGAAATAA WNGSGSGY TATGGCATGG NSATSSSGSGGTGCTGCTC GS TTGGCGCTCCT GGCGGATTAG GATCAGCAGC TTTGGGGGCC GCGGGAGGTGCATTACAAAC TGTAGGGCAA GGATTAATTG ACCATGGTCC TGTAAATGTC CCCATCCCTGTACTCATCGGG CCAAGCTGGA ATGGTAGCGG TAGTGGTTAT AACAGCGCAA CATCCAGTTCCGGTAGTGGTA GTTAA 204 Microcin Unclassified MREITESQL Escherichia 205ATGCGAGAAA H47 RYISGAGGA coli TAACAGAATC PATSANAAG ACAGTTAAGA AAAIVGALATATATTTCCGG GIPGGPLGV GGCGGGAGGT VVGAVSAGL GCGCCAGCGA TTAIGSTVGSCTTCAGCTAAT GSASSSAGG GCCGCAGGTG GS CTGCAGCTAT TGTTGGAGCT CTCGCCGGAATACCTGGTGG TCCACTTGGG GTTGTAGTTG GAGCCGTATC TGCCGGTTTG ACAACAGCAATTGGCTCGAC CGTGGGAAGT GGTAGTGCCA GTTCTTCTGCT GGTGGCGGTA GCTAA 206Microcin Unclassified MIKHFHFNK Escherichia 207 ATGATTAAGC J25 LSSGKKNNVcoli ATTTTCATTTT PSPAKGVIQI AATAAACTGT KKSASQLTK CTTCTGGTAA GGAGHVPEYAAAAAATAAT FVGIGTPISF GTTCCATCTCC YG TGCAAAGGGG GTTATACAAA TAAAAAAATCAGCATCGCAA CTCACAAAAG GTGGTGCAGG ACATGTGCCT GAGTATTTTGT GGGGATTGGTACACCTATAT CTTTCTATGGC TGA 208 Microcin- Unclassified MYMRELDREscherichia 209 ATGTATATGA 24 EELNCVGGA coli GAGAGTTAGA GDPLADPNSTAGAGAGGAA QIVRQIMSN TTAAATTGCG AAWGPPLVP TTGGTGGGGC ERFRGMAVGTGGAGATCCG AAGGVTQT CTTGCAGATC VLQGAAAH CTAATTCCCA MPVNVPIPK AATTGTAAGAVPMGPSWN CAGATAATGT GSKG CTAATGCGGC ATGGGGCCCG CCTTTGGTGCC AGAGCGGTTTAGGGGAATGG CTGTTGGAGC CGCAGGTGGG GTTACGCAGA CAGTTCTTCAA GGAGCAGCAGCTCATATGCC GGTTAATGTC CCTATACCTA AAGTTCCGAT GGGACCCTCA TGGAACGGAAGTAAAGGATAA 210 Mundticin Unclassified MSQVVGGK Enterococcus 211ATGTCACAGG KS YYGNGVSC mundtii TAGTAGGTGG NKKGCSVD AAAATACTAC WGKAIGIIGNGGTAATGGAG NSAANLATG TCTCATGTAAT GAAGWKS AAAAAAGGGT GCAGTGTTGATTGGGGAAAA GCGATTGGCA TTATTGGAAA TAATTCTGCTG CGAATTTAGC TACTGGTGGAGCAGCTGGTT GGAAAAGTTAA 212 Mundticin L class MKKLTSKE Enterococcus 213TTGAAGAAAT IIA/YG MAQVVGGK mundtii TAACATCAAA NGV YYGNGLSCN AGAAATGGCAKKGCSVDW CAAGTAGTAG GKAIGIIGNN GTGGGAAATA SAANLATGG CTACGGTAAT AAGWKSGGATTATCAT GTAATAAAAA AGGGTGCAGT GTTGATTGGG GAAAAGCTAT TGGCATTATTGGAAATAATT CTGCTGCGAA TTTAGCTACTG GTGGAGCAGC TGGTTGGAAA AGTTAA 214Mutacin Lantibiotic MSNTQLLEV Streptococcus 215 ATGTCAAACA 1140LGTETFDVQ mutans CACAATTATT (Mutacin EDLFAFDTT AGAAGTCCTT III) DTTIVASNDGGTACTGAAA DPDTRFKSW CTTTTGATGTT SLCTPGCAR CAAGAAGATC TGSFNSYCCTCTTTGCTTTT GATACAACAG ATACTACTATT GTGGCAAGCA ACGACGATCC AGATACTCGTTTCAAAAGTT GGAGCCTTTG TACGCCTGGT TGTGCAAGGA CAGGTAGTTT CAATAGTTACTGTTGCTGA 216 Mutacin-2 Lantibiotic MNKLNSNA Streptococcus 217ATGAACAAGT VVSLNEVSD mutans TAAACAGTAA SELDTILGGN CGCAGTAGTT RWWQGVVPTCTTTGAATG TVSYECRMN AAGTTTCAGA SWQHVFTCC TTCTGAATTG GATACTATTTTGGGTGGTAAT CGTTGGTGGC AAGGTGTTGT GCCAACGGTC TCATATGAGT GTCGCATGAATTCATGGCAA CATGTTTTCAC TTGCTGTTAA 218 Nisin A Lantibiotic MSTKDFNLDLactococcus 219 ATGAGTACAA LVSVSKKDS lactis subsp. AAGATTTTAAGASPRITSISL lactis CTTGGATTTG CTPGCKTGA (Streptococcus GTATCTGTTTCLMGCNMKT lactis) GAAGAAAGAT ATCHCSIHV TCAGGTGCAT SK CACCACGCATTACAAGTATTT CGCTATGTAC ACCCGGTTGT AAAACAGGAG CTCTGATGGG TTGTAACATGAAAACAGCAA CTTGTCATTGT AGTATTCACG TAAGCAAATAA 220 Nisin F LantibioticMSTKDFNLD Lactococcus 221 ATGAGTACAA LVSVSKKDS lactis AAGATTTCAAGASPRITSISL CTTGGATTTG CTPGCKTGA GTATCTGTTTC LMGCNMKT GAAGAAAGATATCNCSVHV TCAGGTGCAT SK CACCACGCAT TACAAGTATTT CGCTATGTAC ACCCGGTTGTAAAACAGGAG CTCTGATGGG TTGTAACATG AAAACAGCAA CTTGTAATTGT AGCGTTCACGTAAGCAAA 222 Nisin Q Lantibiotic MSTKDFNLD Lactococcus 223 ATGAGTACAALVSVSKTDS lactis AAGATTTCAA GASTRITSIS CTTAGATTTG LCTPGCKTG GTATCTGTTTCVLMGCNLKT AAAAACAGAT ATCNCSVHV TCTGGCGCTTC SK AACACGTATT ACCAGCATTTCGCTTTGTAC ACCAGGTTGT AAAACAGGTG TTCTGATGGG ATGTAACCTG AAAACAGCAACTTGTAATTGT AGCGTTCACG TAAGCAAATAA 224 Nisin U Lantibiotic MNNEDFNLStreptococcus 225 ATGAACAATG DLIKISKENN uberis AAGATTTTAA SGASPRITSKTTTGGATCTCA SLCTPGCKT TCAAAATCTC GILMTCPLK AAAGGAAAAC TATCGCHFGAACTCAGGAG CTTCACCTCGA ATAACTAGTA AATCATTATGT ACTCCTGGAT GTAAGACGGGTATTTTGATGA CTTGTCCACTA AAAACTGCAA CCTGTGGTTG TCATTTTGGAT AA 226 Nisin ZLantibiotic MSTKDFNLD Lactococcus 227 ATGAGTACAA LVSVSKKDS lactis subsp.AAGATTTTAA GASPRITSISL lactis CTTGGATTTG CTPGCKTGA (StreptococcusGTATCTGTTTC LMGCNMKT lactis) GAAGAAAGAT ATCNCSIHV TCAGGTGCAT SKCACCACGCAT TACAAGTATTT CGCTATGTAC ACCCGGTTGT AAAACAGGAG CTCTGATGGGTTGTAACATG AAAACAGCAA CTTGTAATTGT AGTATTCACG TAAGCAAATAA 228 NukacinLantibiotic MENSKVMK Staphylococcus 229 ATGGAAAATT ISK-1 DIEVANLLEwarneri CTAAAGTTAT EVQEDELNE GAAGGACATT VLGAKKKSG GAAGTAGCAA VIPTVSHDCATTTATTAGA HIMNSFQFVF AGAGGTTCAA TCCS GAAGATGAAT TGAATGAAGT CTTAGGAGCTAAGAAAAAGT CAGGAGTAAT CCCAACTGTG TCACACGATT GCCATATGAA TTCTTTCCAATTTGTATTTACT TGTTGTTCATAA 230 Paenicidin A Lantibiotic MAENLFDLDPaenibacillus 231 ATGGCTGAAA IQVNKSQGS polymyxa ACTTATTTGAT VEPQVLSIV(Bacillus CTGGACATTC ACSSGCGSG polymyxa) AAGTAAACAA KTAASCVET ATCTCAAGGTCGNRCFTNV TCTGTAGAGC GSLC CTCAGGTTCT GAGCATTGTT GCATGTTCTA GCGGATGTGGTAGCGGTAAA ACAGCTGCCA GTTGTGTTGA AACTTGTGGC AACCGGTGCT TTACTAACGTTGGTTCACTCT GCTAA 232 Pediocin class MKKIEKLTE Pediococcus 233 ATGAAAAAAAPA-1 IIA/YG KEMANIIGG acidilactici TTGAAAAATT (Pediocin NGV KYYGNGVTAACTGAAAAA ACH) CGKHSCSVD GAAATGGCCA WGKATTCII ATATCATTGG NNGAMAWATGGTAAATAC TGGHQGNH TACGGTAATG KC GGGTTACTTG TGGCAAACAT TCCTGCTCTGTTGACTGGGGT AAGGCTACCA CTTGCATAATC AATAATGGAG CTATGGCATG GGCTACTGGTGGACATCAAG GTAATCATAA ATGCTAG 234 Penocin A class MTEIKVLND Pediococcus235 ATGACTGAAA IIA/YG KELKNVVGG pentosaceus TTAAAGTACT NGV KYYGNGVH(strain ATCC AAACGATAAG CGKKTCYVD 25745/183- GAACTAAAAA WGQATASIG 1w)ATGTCGTAGG KIIVNGWTQ AGGAAAGTAT HGPWAHR TACGGTAACG GAGTGCATTG TGGTAAAAAGACTTGCTATGT GGACTGGGGA CAAGCTACAG CTAGCATTGG AAAAATTATA GTGAACGGATGGACACAACA CGGGCCTTGG GCACATAGAT AA 236 Pep5 Lantibiotic MKNNKNLFStaphylococcus 237 ATGAAAAATA DLEIKKETSQ epidermidis ACAAAAATTTNTDELEPQT ATTTGATTTAG AGPAIRASV AAATTAAAAA KQCQKTLKA AGAAACAAGTTRLFTVSCK CAAAACACTG GKNGCK ATGAACTTGA ACCTCAAACT GCTGGACCAG CGATTAGAGCTTCTGTGAAA CAATGTCAGA AAACTTTGAA AGCTACGCGT TTATTTACAGT GTCTTGCAAAGGAAAAAACG GATGTAAATAG 238 Piscicolin class MKTVKELSV Carnobacterium 239ATGAAAACTG 126 IIA/YG KEMQLTTGG maltaromaticum TTAAAGAACT NGV KYYGNGVS(Carnobacterium TAGCGTTAAA CNKNGCTV piscicola) GAAATGCAAC DWSKAIGIIGTAACTACAGG NNAAANLTT AGGTAAGTAT GGAAGWNKG TACGGAAATG GCGTTTCCTGTAATAAAAATG GTTGTACTGT AGATTGGAGC AAAGCTATTG GGATTATAGG AAACAATGCAGCAGCAAATT TGACTACAGG TGGAGCCGCT GGTTGGAACA AAGGATAA 240 PlantaricinUnclassified MYKELTVDE Lactobacillus 241 ATGTATAAAG 1.25 β LALIDGGKKplantarum AATTAACAGT KKKKVACT TGATGAATTA WGNAATAA GCATTGATTG ASGAVXGILATGGAGGAAA GGPTGALAG AAAGAAGAAG AIWGVSQCA AAAAAAGTAG SNNLHGMHCTTGTACTTGG GGAAATGCAG CAACAGCCGC TGCTTCTGGT GCAGTTANGG GTATTCTTGGTGGGCCTACTG GTGCACTGGC TGGAGCTATC TGGGGCGTTT CACAATGCGC GTCTAACAACTTACACGGCA TGCACTAA 242 Plantaricin class IIa MMKKIEKLT Lactobacillus243 ATGATGAAAA 423 EKEMANIIG plantarum AAATTGAAAA GKYYGNGV ATTAACTGAATCGKHSCSV AAAGAAATGG NWGQAFSCS CCAATATCATT VSHLANFGH GGTGGTAAAT GKCACTATGGTAA TGGGGTTACT TGTGGTAAAC ATTCCTGCTCT GTTAACTGGG GCCAAGCATTTTCTTGTAGTG TGTCACATTTA GCTAACTTCG GTCATGGAAA GTGCTAA 244 PlantaricinUnclassified MSKLVKTLT Lactobacillus 245 ATGAGTAAAC ASM1 VDEISKIQTNplantarum TAGTTAAAAC GGKPAWCW ATTAACTGTC YTLAMCGA GATGAAATCT GYDSGTCDYCTAAGATTCA MYSHCFGVK AACCAATGGT HSSGGGGSY GGAAAACCTG HC CATGGTGTTGGTACACATTG GCAATGTGCG GTGCTGGTTA TGATTCAGGC ACTTGTGATT ATATGTATTCACACTGCTTTG GTGTAAAACA CTCTAGCGGT GGTGGCGGTA GCTACCATTG TTAG 246Plantaricin E Unclassified MLQFEKLQY Lactobacillus 247 ATGCTACAGTSRLPQKKLA plantarum TTGAGAAATT KISGGFNRG ACAATATTCC GYNFGKSVR AGGTTGCCGCHVVDAIGSV AAAAAAAGCT AGIRGILKSIR TGCCAAAATA TCTGGTGGTTT TAATCGGGGCGGTTATAACT TTGGTAAAAG TGTTCGACAT GTTGTTGATG CAATTGGTTC AGTTGCAGGCATTCGTGGTA TTTTGAAAAG TATTCGTTAA 248 Plantaricin F Class IIb MKKFLVLRDLactobacillus 249 ATGAAAAAAT RELNAISGG plantarum TTCTAGTTTTG VFHAYSARGCGTGACCGTG VRNNYKSAV AATTAAATGC GPADWVISA TATTTCAGGT VRGFIHG GGCGTTTTCCATGCCTATAG CGCGCGTGGC GTTCGGAATA ATTATAAAAG TGCTGTTGGG CCTGCCGATTGGGTCATTAG CGCTGTCCGA GGATTCATCC ACGGATAG 250 Plantaricin J Class IIbMTVNKMIK Lactobacillus 251 ATGACTGTGA DLDVVDAFA plantarum ACAAAATGATPISNNKLNG TAAGGATTTG VVGGGAWK GATGTAGTAG NFWSSLRKG ATGCATTTGC FYDGEAGRAACCTATTTCTA IRR ATAATAAGTT GAACGGGGTT GTTGGGGGAG GCGCTTGGAA AAATTTCTGGTCTAGTTTAA GAAAAGGATT TTATGATGGC GAAGCTGGCA GAGCAATCCG TCGTTAA 252Plantaricin K Unclassified MKIKLTVLN Lactobacillus 253 ATGAAAATTAEFEELTADA plantarum AATTAACTGTT EKNISGGRR TTAAATGAAT SRKNGIGYAITTGAAGAATT GYAFGAVER AACTGCTGAC AVLGGSRDY GCTGAAAAGA NK ATATTTCTGGTGGCCGTCGGA GTCGTAAAAA TGGAATTGGA TACGCTATTG GTTATGCGTTT GGCGCGGTTGAACGGGCCGT GCTTGGTGGT TCAAGGGATT ATAATAAGTGA 254 PlantaricinUnclassified MDKFEKIST Lactobacillus 255 ATGGATAAAT NC8α SNLEKISGGplantarum TTGAAAAAAT DLTTKLWSS TAGTACATCT WGYYLGKK AACCTAGAAA ARWNLKHPAGATCTCTGG YVQF CGGTGATTTA ACAACCAAGT TATGGAGCTC TTGGGGATAT TATCTTGGCAAGAAAGCACG TTGGAATTTA AAGCACCCAT ATGTTCAATTT 256 PlantaricinUnclassified MNNLNKFST Lactobacillus 257 ATGAATAACT NC8β LGKSSLSQIEplantarum TGAATAAATT GGSVPTSVY TTCTACTCTAG TLGIKILWSA GCAAGAGTAGYKHRKTIEK CTTGTCTCAAA SFNKGFYH TTGAGGGCGG ATCAGTCCCA ACTTCAGTATATACGCTTGG AATTAAAATT CTATGGTCTG CGTATAAGCA TCGCAAAACG ATTGAAAAAAGTTTTAATAA AGGCTTTTATC ATTAA 258 Plantaricin Unclassified MNNALSFEQLactobacillus 259 ATGAATAACG Sα QFTDFSTLSD plantarum CATTAAGTTTTSELESVEGG GAACAACAAT RNKLAYNM TTACAGACTTC GHYAGKATI AGCACCTTATFGLAAWALLA CGGACTCTGA ATTAGAATCC GTTGAGGGTG GCCGAAATAA GCTTGCATATAATATGGGGC ATTACGCTGG TAAGGCAACC ATTTTTGGACT TGCAGCATGG GCACTCCTTG CATGA260 Plantaricin Unclassified MDKIIKFQGI Lactobacillus 261 ATGGATAAGA SβSDDQLNAVI plantarum TTATTAAGTTT GGKKKKQS CAAGGGATTT WYAAAGDAI CTGATGATCAVSFGEGFLN ATTAAATGCT AW GTTATCGGTG GGAAAAAGAA AAAACAATCT TGGTACGCAGCAGCTGGTGA TGCAATCGTT AGTTTTGGTG AAGGATTTTT AAATGCTTGG TAA 262Plantaricin Lantibiotic MKISKIEAQ Lactobacillus 263 ATGAAAATTT Wα (two-ARKDFFKKI plantarum CTAAGATTGA peptide) DTNSNLLNV AGCTCAGGCT NGAKCKWWCGTAAAGATT NISCDLGNN TTTTTAAAAA GHVCTLSHE AATCGATACT CQVSCN AACTCGAACTTATTAAATGT AAATGGTGCC AAATGCAAGT GGTGGAATAT TTCGTGTGATT TAGGAAATAATGGCCATGTTT GTACCTTGTC ACATGAATGC CAAGTATCTT GTAACTAA 264 PlantaricinLantibiotic MTKTSRRKN Lactobacillus 265 ATGACTAAAA Wβ (two- AIANYLEPVplantarum CTAGTCGTCG peptide) DEKSINESFG TAAGAATGCT AGDPEARSGATTGCTAATTA IPCTIGAAVA TTTAGAACCA ASIAVCPTTK GTCGACGAAA CSKRCGKRKKAAAGTATTAA TGAATCTTTTG GGGCTGGGGA TCCGGAAGCA AGATCCGGAA TTCCATGTACAATCGGCGCAG CTGTCGCAGC ATCAATTGCA GTTTGTCCAA CTACTAAGTG TAGTAAACGTTGTGGCAAGC GTAAGAAATAA 266 Plantaricin-A Unclassified MKIQIKGMKLactobacillus 267 ATGAAAATTC QLSNKEMQK plantarum AAATTAAAGG IVGGKSSAY(strain ATCC TATGAAGCAA SLQMGATAI BAA-793/ CTTAGTAATA KQVKKLFKK NCIMBAGGAAATGCA WGW 8826/ AAAAATAGTA WCFS1) GGTGGAAAGA GTAGTGCGTA TTCTTTGCAGATGGGGGCAAC TGCAATTAAA CAGGTAAAGA AACTGTTTAA AAAATGGGGA TGGTAA 268Propionicin Unclassified MNKTHKMA Propionibacterium 269 ATGAACAAAA SM1TLVIAAILAA jensenii CACACAAAAT GMTAPTAYA GGCGACGCTG DSPGNTRITAGTAATTGCCG SEQSVLTQIL CGATCTTGGC GHKPTQTEY CGCCGGAATG NRYVETYGSACCGCACCAA VPTEADINA CTGCCTATGC YIEASESEGS AGATTCTCCT SSQTAAHDDGGAAACACCA STSPGTSTEI GAATTACAGC YTQAAPARF CAGCGAGCAA SMFFLSGTWAGCGTCCTTA ITRSGVVSLS CCCAGATACT LKPRKGGIG CGGCCACAAA NEGDERTWCCTACACAAA KTVYDKFHN CTGAATATAA AGQWTRYK CCGATACGTT NNGVDASM GAGACTTACGKKQYMCHF GAAGCGTACC KYGMVKTP GACCGAAGCA WNLEPHKK GACATCAACG AADVSPVKCNCATATATAGA AGCGTCTGAA TCTGAGGGAT CATCAAGTCA AACGGCTGCT CACGATGACTCGACATCACC CGGCACGAGT ACCGAAATCT ACACGCAGGC AGCCCCTGCC AGGTTCTCAATGTTTTTCCTG TCCGGAACTT GGATCACTAG GAGTGGTGTA GTATCGCTCTC CTTGAAGCCAAGGAAGGGTG GTATTGGCAA CGAGGGGGAC GAGCGTACCT GGAAGACTGT ATACGACAAATTCCATAACG CTGGGCAATG GACACGATAC AAGAACAACG GCGTAGACGC CAGCATGAAAAAGCAGTACA TGTGCCACTTC AAGTACGGGA TGGTGAAGAC GCCATGGAAT CTGGAGCCCCACAAGAAGGC TGCAGACGTC AGTCCAGTCA AGTGCAACTAG 270 PropionicinUnclassified MKKTLLRSG Propionibacterium 271 ATGAAGAAGA T1 TIALATAAAFthoenii CCCTCCTGCG GASLAAAPS AAGTGGAACG AMAVPGGC ATCGCACTGG TYTRSNRDVCGACCGCGGC IGTCKTGSG TGCATTTGGC QFRIRLDCN GCATCATTGG NAPDKTSVWCAGCCGCCCC AKPKVMVS ATCTGCCATG VHCLVGQPR GCCGTTCCTG SISFETK GTGGTTGCACGTACACAAGA AGCAATCGCG ACGTCATCGG TACCTGCAAG ACTGGAAGCG GCCAGTTCCGAATCCGACTT GACTGCAACA ACGCTCCAGA CAAAACTTCA GTCTGGGCCA AGCCCAAGGTAATGGTGTCG GTTCACTGTCT TGTTGGTCAA CCGAGGTCCA TCTCGTTCGA GACCAAGTGA 272Propionicin-F Unclassified MNTKAVNL Propionibacterium 273 ATGAATACCAKSENTTKLV freudenreichii AAGCTGTAAA SYLTENQLD subsp. TCTGAAGTCAEFIRRIRIDG freudenreichii GAAAACACGA ALVEEVSQN CTAAGTTGGT AKQALDNTGGAGCTACCTT LNGWINTDC ACGGAAAATC DEGLLSDFIS AATTGGATGA KIASARWIPLGTTTATTAGA AESIRPAVTD AGGATTCGCA RDKYRVSC TTGATGGCGC WFYQGMNI TCTTGTGGAAAIYANIGGV GAGGTCAGTC ANIIGYTEAA AAAATGCTAA VATLLGAVV GCAGGCCTTAAVAPVVPGT GATAATACTG PTPPKDKSS GGCTCAATGG QYKEVPLAV CTGGATAAAT RLSETYHEEACTGATTGCG GVRGLFDEL ATGAAGGCCT NYSESRMIS TCTCTCTGATT TLRRASTDGTCATTTCAAA VLINSWNDG GATAGCAAGT QDTILLKKY GCTAGATGGA NFQDLQLTVTTCCATTAGCT RSRIVGNQTI GAGTCAATTC IEECKITDGR GACCTGCGGT KTLSDETVGACTGACAGG GATAAGTATC GAGTAAGTTG CTGGTTCTACC AGGGGATGAA TATAGCAATTTACGCAAATAT CGGTGGCGTG GCCAATATTA TCGGCTATAC GGAGGCCGCA GTCGCAACACTCCTTGGTGC AGTTGTGGCG GTAGCTCCTG TGGTCCCTGG AACTCCAACC CCTCCAAAGGACAAGAGTTC GCAATATAAG GAGGTTCCCC TTGCCGTTCGT CTTTCCGAAA CATACCACGAAGAGGGAGTA CGAGGTCTAT TCGACGAGCT GAACTACTCC GAGAGCCGTA TGATCTCTACTCTAAGGCGAG CATCAACCGA TGGAGTCCTA ATTAATTCTTG GAACGATGGG CAGGATACAATTCTGCTTAAG AAGTACAATT TCCAAGACTT GCAACTGACT GTCAGGAGCC GCATTGTTGGGAATCAAACA ATAATTGAAG AATGCAAAAT CACTGATGGT AGAAAAACTC TTTCAGACGAGACTGTGTAG 274 Pyocin S1 Unclassified MARPIADLIH Pseudomonas 275ATGGCACGAC FNSTTVTAS aeruginosa CCATTGCTGA GDVYYGPG CCTTATCCACTGGTGIGPIAR TCAACTCTAC PIEHGLDSST AACTGTCACG ENGWQEFES GCAAGCGGAGYADVGVDP ACGTTTATTAC RRYVPLQVK GGCCCTGGGG EKRREIELQF GAGGTACCGGRDAEKKLEA CATTGGCCCC SVQAELDKA ATTGCCAGAC DAALGPAKN CTATAGAGCALAPLDVINRS CGGCTTGGAT LTIVGNALQ TCGTCCACTG QKNQKLLLN AAAATGGCTGQKKITSLGA GCAAGAGTTT KNFLTRTAE GAAAGTTATG EIGEQAVRE CTGATGTGGG GNINGPEAYCGTTGACCCC MRFLDREME AGACGCTATG GLTAAYNVK TTCCTCTTCAG LFTEAISSLQIGTTAAAGAAA RMNTLTAAK AACGCAGGGA ASIEAAAAN GATCGAGCTT KAREQAAAECAGTTCCGAG AKRKAEEQA ATGCCGAGAA RQQAAIRAA AAAACTTGAG NTYAMPAN GCGTCGGTACGSVVATAAG AAGCCGAGCT RGLIQVAQG GGATAAGGCT AASLAQAIS GATGCCGCTC DAIAVLGRVTTGGTCCGGC LASAPSVMA AAAGAATCTT VGFASLTYS GCACCATTGG SRTAEQWQ ACGTCATCAADQTPDSVRY CCGCAGTCTG ALGMDAAK ACCATCGTTG LGLPPSVNL GAAACGCCCT NAVAKASGTCCAGCAAAAG VDLPMRLTN AATCAAAAAC EARGNTTTL TACTGCTGAA SVVSTDGVSTCAGAAGAAG VPKAVPVRM ATTACCAGCC AAYNATTGL TGGGTGCAAA YEVTVPSTTGAATTTCCTTA AEAPPLILTW CCCGTACGGC TPASPPGNQ GGAAGAGATC NPSSTTPVVPGGTGAACAAG KPVPVYEGA CGGTGCGAGA TLTPVKATP AGGCAATATT ETYPGVITLPAACGGGCCTG EDLIIGFPAD AAGCCTATAT SGIKPIYVMF GCGCTTCCTC RDPRDVPGAGACAGGGAAA ATGKGQPVS TGGAAGGTCT GNWLGAAS CACGGCAGCT QGEGAPIPSQTATAACGTAA IADKLRGKT AACTCTTCACC FKNWRDFRE GAAGCGATCA QFWIAVANDGTAGTCTCCA PELSKQFNP GATCCGCATG GSLAVMRD AATACGTTGA GGAPYVRES CCGCCGCCAAEQAGGRIKIE AGCAAGTATT IHHKVRVAD GAGGCGGCCG GGGVYNMG CAGCAAACAA NLVAVTPKRGGCGCGTGAA HIEIHKGGK CAAGCAGCGG CTGAGGCCAA ACGCAAAGCC GAAGAGCAGGCCCGCCAGCA AGCGGCGATA AGAGCTGCCA ATACCTATGC CATGCCGGCC AATGGCAGCGTTGTCGCCAC CGCCGCAGGC CGGGGTCTGA TCCAGGTCGC ACAAGGCGCC GCATCCCTTGCTCAAGCGAT CTCCGATGCG ATTGCCGTCCT GGGCCGGGTC CTGGCTTCAG CACCCTCGGTGATGGCCGTG GGCTTTGCCA GTCTGACCTA CTCCTCCCGG ACTGCCGAGC AATGGCAGGACCAAACGCCC GATAGCGTTC GTTACGCCCT GGGCATGGAT GCCGCTAAAT TGGGGCTTCCCCCAAGCGTA AACCTGAACG CGGTTGCAAA AGCCAGCGGT ACCGTCGATC TGCCGATGCGCCTGACCAAC GAGGCACGAG GCAACACGAC GACCCTTTCG GTGGTCAGCA CCGATGGTGTGAGCGTTCCG AAAGCCGTTC CGGTCCGGAT GGCGGCCTAC AATGCCACGA CAGGCCTGTACGAGGTTACG GTTCCCTCTAC GACCGCAGAA GCGCCGCCAC TGATCCTGAC CTGGACGCCGGCGAGTCCTC CAGGAAACCA GAACCCTTCG AGTACCACTC CGGTCGTACC GAAGCCGGTGCCGGTATATG AGGGAGCGAC CCTTACACCG GTGAAGGCTA CCCCGGAAAC CTATCCTGGGGTGATTACAC TACCGGAAGA CCTGATCATC GGCTTCCCGG CCGACTCGGG GATCAAGCCGATCTATGTGA TGTTCAGGGA TCCGCGGGAT GTACCTGGTG CTGCGACTGG CAAGGGACAGCCCGTCAGCG GTAATTGGCT CGGCGCCGCC TCTCAAGGTG AGGGGGCTCC AATTCCAAGCCAGATTGCGG ATAAACTACG TGGTAAGACA TTCAAAAACT GGCGGGACTT TCGGGAACAATTCTGGATAG CTGTGGCTAA TGATCCTGAG TTAAGTAAAC AGTTTAATCCT GGTAGTTTAGCTGTAATGAG AGATGGAGGG GCTCCTTATGT CAGAGAGTCA GAACAGGCTG GCGGGAGAATAAAGATCGAA ATCCACCACA AGGTTCGAGT AGCAGATGGA GGCGGCGTTT ACAATATGGGGAACCTTGTT GCAGTAACGC CAAAACGTCA TATAGAAATC CACAAGGGAG GGAAGTGA 276Pyocin S2 colicin/pyosin MAVNDYEP Pseudomonas 277 ATGGCTGTCA nucleaseGSMVITHVQ aeruginosa ATGATTACGA family GGGRDIIQYI (strain ATCCACCTGGTTCG PARSSYGTPP 15692/ ATGGTTATTA FVPPGPSPYV PAO1/1C/ CACATGTGCAGTGMQEYR PRS 101/ GGGTGGTGGG KLRSTLDKS LMG 12228) CGTGACATAA HSELKKNLKTCCAGTATATT NETLKEVDE CCTGCTCGAT LKSEAGLPG CAAGCTACGG KAVSANDIRTACTCCACCAT DEKSIVDAL TTGTCCCACCA MDAKAKSL GGACCAAGTC KAIEDRPANCGTATGTCGG LYTASDFPQ TACTGGAATG KSESMYQSQ CAGGAGTACA LLASRKFYGGGAAGCTAAG EFLDRHMSE AAGTACGCTT LAKAYSADI GATAAGTCCC YKAQIAILKATTCAGAACT QTSQELENK CAAGAAAAAC ARSLEAEAQ CTGAAAAATG RAAAEVEADAAACCCTGAA YKARKANV GGAGGTTGAT EKKVQSELD GAACTCAAGA QAGNALPQL GTGAAGCGGGTNPTPEQWL GTTGCCAGGT ERATQLVTQ AAAGCGGTCA AIANKKKLQ GTGCCAATGA TANNALIAKCATCCGCGAT APNALEKQK GAAAAGAGTA ATYNADLLV TCGTTGATGC DEIASLQARLACTCATGGAT DKLNAETAR GCCAAAGCAA RKEIARQAAI AATCGCTAAA RAANTYAMGGCCATTGAG PANGSVVAT GATCGCCCGG AAGRGLIQV CCAATCTTTAT AQGAASLAQACGGCTTCAG AISDAIAVLG ACTTTCCTCAG RVLASAPSV AAGTCAGAGT MAVGFASLTCGATGTACCA YSSRTAEQW GAGTCAGTTG QDQTPDSVR CTGGCCAGCC YALGMDAA GAAAATTCTAKLGLPPSVN TGGAGAGTTC LNAVAKASG CTGGATCGCC TVDLPMRLT ATATGAGTGA NEARGNTTTGCTGGCCAAA LSVVSTDGV GCGTACAGCG SVPKAVPVR CCGATATCTAT MAAYNATTAAGGCGCAAA GLYEVTVPS TCGCTATCTTG TTAEAPPLIL AAACAAACGT TWTPASPPGCTCAAGAGCT NQNPSSTTP GGAGAATAAA VVPKPVPVY GCCCGGTCAT EGATLTPVKTGGAAGCAGA ATPETYPGVI AGCCCAGCGA TLPEDLIIGFP GCCGCTGCTG ADSGIKPIYVAGGTGGAGGC MFRDPRDVP GGACTACAAG GAATGKGQP GCCAGGAAGG VSGNWLGA CAAATGTCGAASQGEGAPIP GAAAAAAGTG SQIADKLRG CAGTCCGAGC KTFKNWRDF TTGACCAGGCREQFWIAVA TGGGAATGCT NDPELSKQF TTGCCTCAACT NPGSLAVMR GACCAATCCADGGAPYVRE ACGCCAGAGC SEQAGGRIKI AGTGGCTTGA EIHHKVRIA ACGCGCTACT DGGGVYNMCAACTGGTTA GNLVAVTPK CGCAGGCGAT RHIEIHKGGK CGCCAATAAG AAGAAATTGCAGACTGCAAA CAATGCCTTG ATTGCCAAGG CACCCAATGC ACTGGAGAAA CAAAAGGCAACCTACAACGC CGATCTCCTA GTGGATGAAA TCGCCAGCCT GCAAGCACGG CTGGACAAGCTGAACGCCGA AACGGCAAGG CGCAAGGAAA TCGCTCGTCA AGCGGCGATC AGGGCTGCCAATACTTATGCC ATGCCAGCCA ATGGCAGCGT TGTCGCCACC GCCGCAGGCC GGGGTCTGATCCAGGTCGCA CAAGGCGCCG CATCCCTTGCT CAAGCGATCT CCGATGCGAT TGCCGTCCTGGGCCGGGTCC TGGCTTCAGC ACCCTCGGTG ATGGCCGTGG GCTTTGCCAG TCTGACCTACTCCTCCCGGAC TGCCGAGCAA TGGCAGGACC AAACGCCCGA TAGCGTTCGTT ACGCCCTGGGCATGGATGCC GCTAAATTGG GGCTTCCCCC AAGCGTAAAC CTGAACGCGG TTGCAAAAGCCAGCGGTACC GTCGATCTGC CGATGCGCCT GACCAACGAG GCACGAGGCA ACACGACGACCCTTTCGGTG GTCAGCACCG ATGGTGTGAG CGTTCCGAAA GCCGTTCCGG TCCGGATGGCGGCCTACAAT GCCACGACAG GCCTGTACGA GGTTACGGTT CCCTCTACGA CCGCAGAAGCGCCGCCACTG ATCCTGACCT GGACGCCGGC GAGTCCTCCA GGAAACCAGA ACCCTTCGAGTACCACTCCG GTCGTACCGA AGCCGGTGCC GGTATATGAG GGAGCGACCC TTACACCGGTGAAGGCTACC CCGGAAACCT ATCCTGGGGT GATTACACTA CCGGAAGACC TGATCATCGGCTTCCCGGCC GACTCGGGGA TCAAGCCGAT CTATGTGATG TTCAGGGATC CGCGGGATGTACCTGGTGCT GCGACTGGCA AGGGACAGCC CGTCAGCGGT AATTGGCTCG GCGCCGCCTCTCAAGGTGAG GGGGCTCCAA TTCCAAGCCA GATTGCGGAT AAACTACGTG GTAAGACATTCAAAAACTGG CGGGACTTTC GGGAACAATT CTGGATAGCT GTGGCTAATG ATCCTGAGTTAAGTAAACAG TTTAATCCTGG TAGTTTAGCT GTAATGAGAG ATGGAGGGGC TCCTTATGTCAGAGAGTCAGA ACAGGCTGGC GGGAGAATAA AGATCGAAAT CCACCACAAG GTTCGAATAGCAGATGGAGG CGGCGTTTAC AATATGGGGA ACCTTGTTGC AGTAACGCCA AAACGTCATATAGAAATCCA CAAGGGAGGG AAGTGA 278 Ruminococcin-A Lantibiotic MRNDVLTLTRuminococcus 279 ATGAGAAATG NPMEEKELE gnavus ACGTATTAAC QILGGGNGVATTAACAAAC LKTISHECN CCAATGGAAG MNTWQFLFT AGAACGAACT CC GGAGCAGATCTTAGGTGGTG GCAATGGTGT GTTAAAAACG ATTAGCCACG AATGCAATAT GAACACATGGCAGTTCCTGTT TACTTGTTGCT AA 280 Sakacin G Class IIa MKNAKSLTILactobacillus 281 ATGAAAAACG QEMKSITGG sakei CAAAAAGCCT KYYGNGVSAACAATTCAA CNSHGCSVN GAAATGAAAT WGQAWTCG CTATTACAGG VNHLANGG TGGTAAATACHGVC TATGGTAATG GCGTTAGCTG TAACTCTCAC GGCTGTTCAG TAAATTGGGG GCAAGCATGGACTTGTGGAG TAAACCATCT AGCTAATGGC GGTCATGGAG TTTGTTAA 282 Sakacin-A classMNNVKELS Lactobacillus 283 ATGAATAATG IIA/YG MTELQTITG sakei TAAAAGAATTNGV GARSYGNG AAGTATGACA VYCNNKKC GAATTACAAA WVNRGEAT CAATTACCGGQSIIGGMISG CGGTGCTAGA WASGLAGM TCATATGGCA ACGGTGTTTA CTGTAATAATAAAAAATGTT GGGTAAATCG GGGTGAAGCA ACGCAAAGTA TTATTGGTGG TATGATTAGCGGCTGGGCTA GTGGTTTAGC TGGAATGTAA 284 Sakacin-P class MEKFIELSLKLactobacillus 285 ATGGAAAAGT (Sakacin IIA/YG EVTAITGGK sakei TTATTGAATTA674) NGV YYGNGVHC TCTTTAAAAG GKHSCTVD AAGTAACAGC WGTAIGNIG AATTACAGGTNNAAANWA GGAAAATATT TGGNAGWNK ATGGTAACGG TGTACACTGT GGAAAACATTCATGTACCGT AGACTGGGGA ACAGCTATTG GAAATATCGG AAATAATGCA GCTGCAAACTGGGCCACAGG CGGAAACGCT GGCTGGAATA AATAA 286 Salivaricin 9 lantibioticMKSTNNQSI Streptococcus 287 ATGAAATCAA AEIAAVNSL salivarius CAAATAATCAQEVSMEELD AAGTATCGCA QIIGAGNGV GAAATTGCAG VLTLTHECN CAGTAAACTC LATWTKKLKACTACAAGAA CC GTAAGTATGG AGGAACTAGA CCAAATTATT GGTGCCGGAA ACGGAGTGGTTCTTACTCTTA CTCATGAATG TAACCTAGCA ACTTGGACAA AAAAACTAAA ATGTTGCTAA 288Salivaricin A Lantibiotic MSFMKNSK Streptococcus 289 ATGAGTTTTATDILTNAIEEV pyogenes GAAAAATTCA SEKELMEVA serotype AAGGATATTT GGKKGSGWM28 (strain TGACTAATGC FATITDDCPN MGAS6180) TATCGAAGAA SVFVCC GTTTCTGAAAAAGAACTTAT GGAAGTAGCT GGTGGTAAAA AAGGTTCCGG TTGGTTTGCA ACTATTACTGATGACTGTCC GAACTCAGTA TTCGTTTGTTG TTAA 290 Salivaricin LantibioticMKNSKDVL Streptococcus 291 ATGAAAAACT A3 NNAIEEVSE salivarius CAAAAGATGTKELMEVAG TTTGAACAAT GKKGPGWIA GCTATCGAAG TITDDCPNSI AGGTTTCTGA FVCCAAAAGAACTT ATGGAAGTAG CTGGTGGTAA AAAAGGTCCA GGTTGGATTG CAACTATTACTGATGACTGTC CAAACTCAAT ATTCGTTTGTT GTTAA 292 Salivaricin- LantibioticMKNSKDILN Streptococcus 293 ATGAAAAACT A sa NAIEEVSEKE salivariusCAAAAGATAT LMEVAGGK TTTGAACAAT RGSGWIATIT GCTATCGAAG DDCPNSVFVAAGTTTCTGA CC AAAAGAACTT ATGGAAGTAG CTGGTGGTAA AAGAGGTTCA GGTTGGATTGCAACTATTACT GATGACTGTC CAAACTCAGT ATTCGTTTGTT GTTAA 294 StaphylococcinLantibiotic MKSSFLEKDI Staphylococcus 295 ATGAAAAGTT C55 (two- EEQVTWFEEaureus CTTTTTTAGAA alpha peptide) VSEQEFDDD AAAGATATAG IFGACSTNTFAAGAACAAGT SLSDYWGNK GACATGGTTC GNWCTATH GAGGAAGTTT ECMSWCK CAGAACAAGAATTTGACGAT GATATTTTTGG AGCTTGTAGT ACAAACACTT TTTCTTTGAGT GACTATTGGGGTAATAAAGG AAATTGGTGT ACTGCTACTC ACGAATGTAT GTCTTGGTGT AAATAA 296Staphylococcin Lantibiotic MKNELGKFL Staphylococcus 297 ATGAAAAATG C55(two- EENELELGK aureus AATTAGGTAA beta peptide) FSESDMLEIT GTTTTTAGAADDEVYAAG GAAAACGAAT TPLALLGGA TAGAGTTAGG ATGVIGYISN TAAATTTTCAGQTCPTTACT AATCAGACAT RAC GCTAGAAATT ACTGATGATG AAGTATATGC AGCTGGAACACCTTTAGCCTT ATTGGGTGGA GCTGCCACCG GGGTGATAGG TTATATTTCTA ACCAAACATGTCCAACAACT GCTTGTACAC GCGCTTGCTAG 298 Streptin lantibiotic MNNTIKDFDStreptococcus 299 ATGAATAACA LDLKTNKKD pyogenes CAATTAAAGA TATPYVGSRCTTTGATCTCG YLCTPGSCW ATTTGAAAAC KLVCFTTTVK AAATAAAAAA GACACTGCTACACCTTATGTT GGTAGCCGTT ACCTATGTAC CCCTGGTTCTT GTTGGAAATT AGTTTGCTTTACAACAACTGT TAAATAA 300 Streptococcin Lantibiotic MEKNNEVIN Streptococcus301 ATGGAAAAAA A- SIQEVSLEEL pyogenes ATAATGAAGT FF22 DQIIGAGKNAATCAACTCT GVFKTISHEC ATTCAAGAAG HLNTWAFLA TTAGTCTTGA TCCS AGAACTCGATCAAATTATCG GTGCTGGAAA AAATGGTGTG TTTAAAACAA TTTCTCATGAG TGTCATTTGAATACATGGGC ATTCCTTGCTA CTTGTTGTTCA TAA 302 Streptococcin LantibioticMTKEHEIINS Streptococcus 303 ATGGAAAAAA A- IQEVSLEELD pyogenesATAATGAAGT M49 QIIGAGKNG serotype AATCAACTCT VFKTISHECH M49 ATTCAAGAAGLNTWAFLAT TTAGTCTTGA CCS AGAACTCGAT CAAATTATCG GTGCTGGAAA AAATGGTGTGTTTAAAACAA TTTCTCATGAG TGTCATTTGA ATACATGGGC ATTCCTTGCTA CTTGTTGCTCA TAA304 Sublancin Lantibiotic MEKLFKEVK Bacillus 305 ATGGAAAAGC 168LEELENQKG subtilis TATTTAAAGA SGLGKAQCA (strain 168) AGTTAAACTAALWLQCASG GAGGAACTCG GTIGCGGGA AAAACCAAAA VACQNYRQF AGGTAGTGGA CRTTAGGAAAAG CTCAGTGTGC TGCGTTGTGG CTACAATGTG CTAGTGGCGG TACAATTGGTTGTGGTGGCG GAGCTGTTGC TTGTCAAAAC TATCGTCAATT CTGCAGATAA 306 SubtilinLantibiotic MSKFDDFDL Bacillus 307 ATGTCAAAGT DVVKVSKQ subtilisTCGATGATTTC DSKITPQWK GATTTGGATG SESLCTPGC TTGTGAAAGT VTGALQTCFCTCTAAACAA LQTLTCNCK GACTCAAAAA ISK TCACTCCGCA ATGGAAAAGT GAATCACTTTGTACACCAGG ATGTGTAACT GGTGCATTGC AAACTTGCTTC CTTCAAACAC TAACTTGTAACTGCAAAATC TCTAAATAA 308 Subtilosin Unclassified MKLPVQQV Bacillus 309TTGAAATTGC YSVYGGKDL subtilis CGGTGCAACA PKGHSHSTM (strain 168)GGTCTATTCG PFLSKLQFLT GTCTATGGGG KIYLLDIHTQ GTAAGGATCT PFFI CCCAAAAGGGCATAGTCATTC TACTATGCCCT TTTTAAGTAA ATTACAATTTT TAACTAAAAT CTACCTCTTGGATATACATAC ACAACCGTTTT TCATTTGA 310 Subtilosin-A Unclassified MKKAVIVENBacillus 311 ATGAAAAAAG KGCATCSIG subtilis CTGTCATTGTA AACLVDGPI (strain168) GAAAACAAAG PDFEIAGAT GTTGTGCAAC GLFGLWG ATGCTCGATC GGAGCCGCTTGTCTAGTGGA CGGTCCTATC CCTGATTTTGA AATTGCCGGT GCAACAGGTC TATTCGGTCTATGGGGGTAA 312 Thermophilin Lantibiotic MMNATENQI Streptococcus 313ATGATGAATG 1277 FVETVSDQE thermophilus CTACTGAAAA LEMLIGGAD CCAAATTTTTGRGWIKTLTK TTGAGACTGT DCPNVISSIC GAGTGACCAA AGTIITACKN GAATTAGAAA CATGTTAATTGGT GGTGCAGATC GTGGATGGAT TAAGACTTTA ACAAAAGATT GTCCAAATGTAATTTCTTCAA TTTGTGCAGG TACAATTATTA CAGCCTGTAA AAATTGTGCT TAA 314Thermophilin Unclassified MKQYNGFE Streptococcus 315 ATGAAGCAGT 13VLHELDLAN thermophilus ATAATGGTTTT VTGGQINWG GAGGTTCTAC SVVGHCIGGATGAACTTGA AIIGGAFSGG CTTAGCAAAT AAAGVGCL GTAACTGGCG VGSGKAIINGTCAAATTAA GL TTGGGGATCA GTTGTAGGAC ACTGTATAGG TGGAGCTATT ATCGGAGGTGCATTTTCAGG AGGTGCAGCG GCTGGAGTAG GATGCCTTGTT GGGAGCGGAA AGGCAATCATAAATGGATTA TAA 316 Thermophilin A Unclassified MNTITICKFD Streptococcus317 ATGAATACAA VLDAELLST thermophilus TAACTATTTGT VEGGYSGKD AAATTTGATGCLKDMGGY TTTTAGATGCT ALAGAGSGA GAACTTCTTTC LWGAPAGG GACAGTTGAG VGALPGAFVGGTGGATACT GAHVGAIAG CTGGTAAGGA GFACMGGMI TTGTTTAAAA GNKFN GACATGGGAGGATATGCATT GGCAGGAGCT GGAAGTGGAG CTCTGTGGGG AGCTCCAGCA GGAGGTGTTGGAGCACTTCC AGGTGCATTT GTCGGAGCTC ATGTTGGGGC AATTGCAGGA GGCTTTGCATGTATGGGTGG AATGATTGGT AATAAGTTTA ACTAA 318 Thiocillin UnclassifiedMSEIKKALN Bacillus 319 ATGAGTGAAA (Micrococcin TLEIEDFDAI cereus (strainTTAAAAAAGC P1) EMVDVDAM ATCC 14579/ ATTAAATACG (Micrococcin PENEALEIMDSM 31) CTTGAAATTG P2) GASCTTCVC AAGATTTTGA (Thiocillin TCSCCTTTGCAATTGAA I) ATGGTTGATG (Thiocillin TTGATGCTAT II) GCCAGAAAAC(Thiocillin GAAGCGCTTG III) AAATTATGGG (Thiocillin AGCGTCATGT IV)ACGACATGCG (Antibiotic TATGTACATG YM- CAGTTGTTGT 266183) ACAACTTGA(Antibiotic YM- 266184) 320 Thuricin two- MEVMNNALI Bacillus 321ATGGAAGTTA CD alpha peptide TKVDEEIGG cereus TGAACAATGC lantibioticNAACVIGCI 95/8201 TTTAATTACAA GSCVISEGIG AAGTAGATGA SLVGTAFTLGGGAGATTGGA GGAAACGCTG CTTGTGTAATT GGTTGTATTG GCAGTTGCGT AATTAGTGAAGGAATTGGTT CACTTGTAGG AACAGCATTT ACTTTAGGTT AA 322 Thuricin two-MEVLNKQN Bacillus 323 ATGGAAGTTT CD beta peptide VNIIPESEEV cereusTAAACAAACA lantibiotic GGWVACVG 95/8201 AAATGTAAAT ACGTVCLAS ATTATTCCAGGGVGTEFAA AATCTGAAGA ASYFL AGTAGGTGGA TGGGTAGCAT GTGTTGGAGC ATGTGGTACAGTATGTCTTGC TAGTGGTGGT GTTGGAACAG AGTTTGCAGC TGCATCTTATT TCCTATAA 324Thuricin- Class IId METPVVQPR Bacillus 325 ATGGAAACAC 17 DWTCWSCLthuringiensis CAGTAGTACA VCAACSVEL ACCAAGGGAT LNLVTAATG TGGACTTGTT ASTASGGAGTTGCTT AGTATGTGCA GCATGTTCTGT GGAATTATTA AATTTAGTTAC TGCGGCAACAGGGGCTAGTA CTGCAAGCTAA 326 Trifolitoxin Unclassified MDNKVAKN Rhizobium327 ATGGATAACA VEVKKGSIK leguminosarum AGGTTGCGAA ATFKAAVLK bv. trifoliiGAATGTCGAA SKTKVDIGG GTGAAGAAGG SRQGCVA GCTCCATCAA GGCGACCTTC AAGGCTGCTGTTCTGAAGTC GAAGACGAAG GTCGACATCG GAGGTAGCCG TCAGGGCTGC GTCGCTTAA 328Ubericin A Class IIa MNTIEKFENI Streptococcus 329 ATGAATACAA KLFSLKKIIGuberis TTGAAAAATT GKTVNYGN TGAAAATATT GLYCNQKKC AAACTTTTTTC WVNWSETAACTAAAGAAA TTIVNNSIM ATTATCGGTG NGLTGGNA GCAAAACTGT GWHSGGRA AAATTATGGTAATGGCCTTT ATTGTAACCA AAAAAAATGC TGGGTAAACT GGTCAGAAAC TGCTACAACAATAGTAAATA ATTCCATCATG AACGGGCTCA CAGGTGGTAA TGCGGGTTGG CACTCAGGCGGGAGAGCATAA 330 Uberolysin Unclassified MDILLELAG Streptococcus 331ATGGACATTT YTGIASGTA uberis TATTAGAACT KKVVDAIDK CGCAGGATAT GAAAFVIISIIACTGGGATAG STVISAGAL CCTCAGGTAC GAVSASADF TGCAAAAAAA IILTVKNYISGTTGTTGATG RNLKAQAVIW CCATTGATAA AGGAGCTGCA GCCTTTGTTAT TATTTCAATTATCTCAACAGT AATTAGTGCG GGAGCATTGG GAGCAGTTTC AGCCTCAGCT GATTTTATTATTTTAACTGTAA AAAATTACAT TAGTAGAAAT TTAAAAGCAC AAGCTGTCAT TTGGTAA 332 UviBUnclassified MDSELFKLM Clostridium 333 ATGGATAGTG ATQGAFAILF perfringensAATTATTTAA SYLLFYVLK GTTAATGGCA ENSKREDKY ACACAAGGAG QNIIEELTELCCTTTGCAATA LPKIKEDVE TTATTTTCGTA DIKEKLNK TTTATTGTTTT ATGTTTTAAAAGAGAATAGT AAAAGAGAAG ATAAGTATCA AAATATAATA GAGGAGCTTA CAGAATTATTGCCAAAAATA AAAGAAGATG TAGAAGATAT AAAAGAAAAA CTTAATAAAT AG 334 VariacinLantibiotic, MTNAFQALD Micrococcus 335 ATGACGAACG Type A EVTDAELDAvarians CATTTCAGGC ILGGGSGVIP ACTGGACGAA TISHECHMN GTCACGGACG SFQFVFTCCSCCGAGCTCGA CGCCATCCTT GGCGGGGGCA GTGGTGTTAT TCCCACGATC AGCCACGAGTGCCACATGAA CTCCTTCCAGT TCGTGTTCACC TGCTGCTCCTGA 336 Zoocin AUnclassified MKRIFFAFLS Streptococcus 337 ATGAAACGTA LCLFIFGTQT equisubsp. TATTTTTTGCT VSAATYTRP zooepidemicus TTCTTAAGTTT LDTGNITTGFATGCTTATTTA NGYPGHVG TATTCGGAAC VDYAVPVGT ACAAACGGTA PVRAVANGTTCTGCAGCTA VKFAGNGA CTTATACTCG NHPWMLWM GCCATTAGAT AGNCVLIQH ACGGGAAATAADGMHTGY TCACTACAGG AHLSKISVST GTTTAACGGA DSTVKQGQII TACCCTGGTC GYTGATGQATGTTGGAGT VTGPHLHFE CGATTATGCA MLPANPNW GTACCCGTTG QNGFSGRID GAACTCCGGTPTGYIANAP TAGAGCAGTT VFNGTTPTE GCAAATGGTA PTTPTTNLKI CAGTCAAATTYKVDDLQKI TGCAGGTAAT NGIWQVRN GGGGCTAATC NILVPTDFT ACCCATGGAT WVDNGIAAGCTTTGGATG DDVIEVTSN GCTGGAAACT GTRTSDQVL GTGTTCTAATT QKGGYFVINCAACATGCTG PNNVKSVGT ACGGGATGCA PMKGSGGLS TACTGGATAT WAQVNFTT GCACACTTATGGNVWLNT CAAAAATTTC TSKDNLLYGK AGTTAGCACA GATAGTACAG TTAAACAAGGACAAATCATA GGTTATACTG GTGCCACCGG CCAAGTTACC GGTCCACATT TGCATTTTGAAATGTTGCCA GCAAATCCTA ACTGGCAAAA TGGTTTTTCTG GAAGAATAGA TCCAACCGGATACATCGCTA ATGCCCCTGT ATTTAATGGA ACAACACCTA CAGAACCTAC TACTCCTACAACAAATTTAA AAATCTATAA AGTTGATGAT TTACAAAAAA TTAATGGTATT TGGCAAGTAAGAAATAACAT ACTTGTACCA ACTGATTTCAC ATGGGTTGAT AATGGAATTG CAGCAGATGATGTAATTGAA GTAACTAGCA ATGGAACAAG AACCTCTGAC CAAGTTCTTCA AAAAGGTGGTTATTTTGTCAT CAATCCTAAT AATGTTAAAA GTGTTGGAAC TCCGATGAAA GGTAGTGGTGGTCTATCTTGG GCTCAAGTAA ACTTTACAAC AGGTGGAAAT GTCTGGTTAA ATACTACTAGCAAAGACAAC TTACTTTACGG AAAATAA 338 Fulvocin-C Unclassified ANCSCSTASMyxococcus 339 GCGAACTGCA DYCPILTFCT fulvus GCTGCAGCAC TGTACSYTPCGCGAGCGAT TGCGTGWV TATTGCCCGA YCACNGNFY TTCTGACCTTT TGCACCACCGGCACCGCGTG CAGCTATACC CCGACCGGCT GCGGCACCGG CTGGGTGTAT TGCGCGTGCAACGGCAACTT TTAT 340 Duramycin-C Lantibiotic CANSCSYGP Streptomyces 341TGCGCGAACA LTWSCDGNTK griseoluteus GCTGCAGCTA TGGCCCGCTG ACCTGGAGCTGCGATGGCAA CACCAAA 342 Duramycin Lantibiotic B CKQSCSFGPFStreptoverticillium 343 TGCAAACAGA (duramycin- TFVCDGNTKgriseoverticillatum GCTGCAGCTT B) TGGCCCGTTT (Leucopeptin) ACCTTTGTGTGCGATGGCAAC ACCAAA 344 Carnocin lantibiotic GSEIQPR Carnobacterium 345GGCAGCGAAA UI49 sp. (strain TTCAGCCGCGC UI49) 346 Lactococcin-Unclassified GTWDDIGQG Lactococcus 347 GGCACCTGGG Gα IGRVAYWVG lactissubsp. ATGATATTGG KAMGNMSD lactis CCAGGGCATT VNQASRINR (StreptococcusGGCCGCGTGG KKKH lactis) CGTATTGGGT GGGCAAAGCG ATGGGCAACA TGAGCGATGTGAACCAGGCG AGCCGCATTA ACCGCAAAAA AAAACAT 348 Lactococcin- UnclassifiedKKWGWLAW Lactococcus 349 AAAAAATGGG Gβ VDPAYEFIK lactis subsp.GCTGGCTGGC GFGKGAIKE lactis GTGGGTGGAT GNKDKWKNI (StreptococcusCCGGCGTATG lactis) AATTTATTAA AGGCTTTGGC AAAGGCGCGA TTAAAGAAGGCAACAAAGAT AAATGGAAAA ACATT 350 Ancovenin Lantibiotic CVQSCSFGPStreptomyces 351 TGCGTGCAGA LTWSCDGNTK sp. (strain GCTGCAGCTT A647P-2)TGGCCCGCTG ACCTGGAGCT GCGATGGCAA CACCAAA 352 Actagardine LantibioticSSGWVCTLT Actinoplanes 353 AGCAGCGGCT (Gardimycin) IECGTVICAC liguriaeGGGTGTGCAC CCTGACCATT GAATGCGGCA CCGTGATTTG CGCGTGC 354 CurvaticinUnclassified YTAKQCLQA Lactobacillus 355 TATACCGCGA FS47 IGSCGIAGTGcurvatus AACAGTGCCT AGAAGGPA GCAGGCGATT GAFVGAXV GGCAGCTGCG VXIGCATTGCGGG CACCGGCGCG GGCGCGGCGG GCGGCCCGGC GGGCGCGTTT GTGGGCGCGNNNGTGGTGNN NATT [IN WHICH NNN = ANY AMINO- ACID CODING TRIPLET] 356Bavaricin- class TKYYGNGV Lactobacillus 357 ACCAAATATT MN IIA/YGYCNSKKCW sakei ATGGCAACGG NGV VDWGQAAG CGTGTATTGC GIGQTVVXG AACAGCAAAAWLGGAIPGK AATGCTGGGT GGATTGGGGC CAGGCGGCGG GCGGCATTGG CCAGACCGTGGTGNNNGGCT GGCTGGGCGG CGCGATTCCG GGCAAA[IN WHICH NNN = ANY AMINO- ACIDCODING TRIPLET] 358 Mutacin Lantibiotic FKSWSFCTP Streptococcus 359TTTAAAAGCT B-Ny266 GCAKTGSFN mutans GGAGCTTTTG SYCC CACCCCGGGCTGCGCGAAAA CCGGCAGCTT TAACAGCTAT TGCTGCTTTAA AAGCTGGAGC TTTTGCACCCCGGGCTGCGCG AAAACCGGCA GCTTTAACAG CTATTGCTGC 360 Mundticin class KYYGNGVSEnterococcus 361 AAATATTATG IIA/YG CNKKGCSVD mundtii GCAACGGCGT NGVWGKAIGIIGN GAGCTGCAAC NSAANLATG AAAAAAGGCT GAAGWSK GCAGCGTGGA TTGGGGCAAAGCGATTGGCA TTATTGGCAA CAACAGCGCG GCGAACCTGG CGACCGGCGG CGCGGCGGGCTGGAGCAAA 362 Bavaricin-A class KYYGNGVH Lactobacillus 363 AAATATTATGIIA/YG XGKHSXTVD sakei GCAACGGCGT NGV WGTAIGNIG GCATNNNGGC NNAAANXAAAACATAGCN TGXNAGG NNACCGTGGA TTGGGGCACC GCGATTGGCA ACATTGGCAACAACGCGGCG GCGAACNNNG CGACCGGCNN NAACGCGGGC GGC [IN WHICH NNN = ANYAMINO- ACID CODING TRIPLET] 364 Lactocin- Class IIb GMSGYIQGILactobacillus 365 GGCATGAGCG 705 PDFLKGYLH paracasei GCTATATTCAGISAANKHK GGGCATTCCG KGRL GATTTTCTGA AAGGCTATCT GCATGGCATT AGCGCGGCGAACAAACATAA AAAAGGCCGC CTG 366 Leucocin-B Unclassified KGKGFWSWLeuconostoc 367 AAAGGCAAAG ASKATSWLT mesenteroides GCTTTTGGAG GPQQPGSPLCTGGGCGAGC LKKHR AAAGCGACCA GCTGGCTGAC CGGCCCGCAG CAGCCGGGCA GCCCGCTGCTGAAAAAACAT CGC 368 Leucocin C class KNYGNGVH Leuconostoc 369 AAAAACTATGIIA/YG CTKKGCSVD mesenteroides GCAACGGCGT NGV WGYAWTNI GCATTGCACCANNSVMNG AAAAAAGGCT LTGGNAGW GCAGCGTGGA HN TTGGGGCTAT GCGTGGACCAACATTGCGAA CAACAGCGTG ATGAACGGCC TGACCGGCGG CAACGCGGGC TGGCATAAC 370 LCIUnclassified AIKLVQSPN Bacillus 371 GCGATTAAAC GNFAASFVL subtilisTGGTGCAGAG DGTKWIFKS CCCGAACGGC KYYDSSKGY AACTTTGCGG WVGIYEVW CGAGCTTTGTDRK GCTGGATGGC ACCAAATGGA TTTTTAAAAGC AAATATTATG ATAGCAGCAA AGGCTATTGGGTGGGCATTT ATGAAGTGTG GGATCGCAAA 372 Lichenin Unclassified ISLEICXIFHDNBacillus 373 ATTAGCCTGG licheniformis AAATTTGCNN NATTTTTCATG ATAAC [INWHICH NNN = ANY AMINO- ACID CODING TRIPLET] 374 Lactococcin classTSYGNGVHC Lactococcus 375 ACCAGCTATG MMFII IIA/YG NKSKCWIDV lactissubsp. GCAACGGCGT NGV SELETYKAG lactis GCATTGCAAC TVSNPKDILW(Streptococcus AAAAGCAAAT lactis) GCTGGATTGA TGTGAGCGAA CTGGAAACCTATAAAGCGGG CACCGTGAGC AACCCGAAAG ATATTCTGTGG 376 Serracin-P Phage-DYHHGVRVL Serratia 377 GATTATCATC Tail- plymuthica ATGGCGTGCG LikeCGTGCTG 378 Halocin- Unclassified DIDITGCSAC Halobacterium 379GATATTGATA C8 KYAAG sp. (strain TTACCGGCTG AS7092) CAGCGCGTGC AAATATGCGGCGGGC 380 Subpeptin Unclassified XXKEIXHIFH Bacillus 381 NNNNNNAAAGJM4-B DN subtilis AAATTNNNCA TATTTTTCATG ATAAC [IN WHICH NNN = ANYAMINO- ACID CODING TRIPLET] 382 Curvalicin- Unclassified TPVVNPPFLLactobacillus 383 ACCCCGGTGG 28a QQT curvatus TGAACCCGCC GTTTCTGCAGCAGACC 384 Curvalicin- Unclassified VAPFPEQFLX Lactobacillus 385GTGGCGCCGT 28b curvatus TTCCGGAACA GTTTCTGNNN [IN WHICH NNN = ANYAMINO-ACID CODING TRIPLET] 386 Curvalicin- Unclassified NIPQLTPTPLactobacillus 387 AACATTCCGC 28c curvatus AGCTGACCCC GACCCCG 388Thuricin-S Unclassified DWTXWSXL Bacillus 389 GATTGGACCN VXAACSVELLthuringiensis NNTGGAGCNN subsp. NCTGGTGNNN entomocidus GCGGCGTGCAGCGTGGAACT GCTG [IN WHICH NNN = ANY AMINO- ACID CODING TRIPLET] 390Curvaticin Unclassified AYPGNGVH Lactobacillus 391 GCGTATCCGG L442CGKYSCTVD curvatus GCAACGGCGT KQTAIGNIG GCATTGCGGC NNAA AAATATAGCTGCACCGTGGA TAAACAGACC GCGATTGGCA ACATTGGCAA CAACGCGGCG 392 Divergicinclass TKYYGNGV Carnobacterium 393 ACCAAATATT M35 IIa/YGN YCNSKKCWdivergens ATGGCAACGG GV VDWGTAQG (Lactobacillus CGTGTATTGC CIDVVIGQLdivergens) AACAGCAAAA GGGIPGKGKC AATGCTGGGT GGATTGGGGC ACCGCGCAGGGCTGCATTGA TGTGGTGATT GGCCAGCTGG GCGGCGGCAT TCCGGGCAAA GGCAAATGC 394Enterocin class IIb NRWYCNSA Enterococcus 395 AACCGCTGGT E-760 AGGVGGAAsp. ATTGCAACAG VCGLAGYV CGCGGCGGGC GEAKENIAG GGCGTGGGCG EVRKGWGMGCGCGGCGGT AGGFTHNKA GTGCGGCCTG CKSFPGSGW GCGGGCTATG ASG TGGGCGAAGCGAAAGAAAAC ATTGCGGGCG AAGTGCGCAA AGGCTGGGGC ATGGCGGGCG GCTTTACCCATAACAAAGCGT GCAAAAGCTT TCCGGGCAGC GGCTGGGCGA GCGGC 396 BacteriocinUnclassified TTKNYGNG Enterococcus 397 ACCACCAAAA E50-52 VCNSVNWCfaecium ACTATGGCAA QCGNVWAS (Streptococcus CGGCGTGTGC CNLATGCAA faecium)AACAGCGTGA WLCKLA ACTGGTGCCA GTGCGGCAAC GTGTGGGCGA GCTGCAACCT GGCGACCGGCTGCGCGGCGT GGCTGTGCAA ACTGGCG 398 Paenibacillin Unclassified ASIIKTTIKVSPaenibacillus 399 GCGAGCATTA KAVCKTLTC polymyxa TTAAAACCAC ICTGSCSNCK(Bacillus CATTAAAGTG polymyxa) AGCAAAGCGG TGTGCAAAAC CCTGACCTGCATTTGCACCG GCAGCTGCAG CAACTGCAAA 400 Epilancin Unclassified SASIVKTTIKStaphylococcus 401 AGCGCGAGCA 15x ASKKLCRGF epidermidis TTGTGAAAACTLTCGCHFT CACCATTAAA GKK GCGAGCAAAA AACTGTGCCG CGGCTTTACC CTGACCTGCGGCTGCCATTTT ACCGGCAAAA AA 402 Enterocin- class IIa KYYGNGVS Enterococcus403 AAATATTATG HF CNKKGCSVD faecium GCAACGGCGT WGKAIGIIGN (StreptococcusGAGCTGCAAC NAAANLTTG faecium) AAAAAAGGCT GKAAWAC GCAGCGTGGA TTGGGGCAAAGCGATTGGCA TTATTGGCAA CAACGCGGCG GCGAACCTGA CCACCGGCGG CAAAGCGGCGTGGGCGTGC 404 Bacillocin Class IIa ATYYGNGL Paenibacillus 405 GCGACCTATT602 YCNKQKHY polymyxa ATGGCAACGG TWVDWNKA (Bacillus CCTGTATTGCSREIGKITVN polymyxa) AACAAACAGA GWVQH AACATTATAC CTGGGTGGAT TGGAACAAAGCGAGCCGCGA AATTGGCAAA ATTACCGTGA ACGGCTGGGT GCAGCAT 406 Bacillocin ClassIIa VNYGNGVS Bacillus 407 GTGAACTATG 1580 CSKTKCSVN circulans GCAACGGCGTWGIITHQAF GAGCTGCAGC RVTSGVASG AAAACCAAAT GCAGCGTGAA CTGGGGCATTATTACCCATC AGGCGTTTCG CGTGACCAGC GGCGTGGCGA GCGGC 408 BacillocinUnclassified FVYGNGVTS Paenibacillus 409 TTTGTGTATG B37 ILVQAQFLVpolymyxa GCAACGGCGT NGQRRFFYT (Bacillus GACCAGCATT PDK polymyxa)CTGGTGCAGG CGCAGTTTCT GGTGAACGGC CAGCGCCGCT TTTTTTATACC CCGGATAAA 410Rhamnosin A Unclassified AVPAVRKTN Lactobacillus 411 GCGGTGCCGG ETLDrhamnosus CGGTGCGCAA AACCAACGAA ACCCTGGAT 412 Lichenicidin A LantibioticMKNSAARE Bacillus 413 ATGAAAAACA A2 (two- AFKGANHPA licheniformisGCGCGGCGCG peptide) GMVSEEELK (strain DSM CGAAGCGTTT ALVGGNDV 13/ATCCAAAGGCGCGA NPETTPATTS 14580) ACCATCCGGC SWTCITAGV GGGCATGGTG TVSASLCPTTAGCGAAGAAG KCTSRC AACTGAAAGC GCTGGTGGGC GGCAACGATG TGAACCCGGA AACCACCCCGGCGACCACCA GCAGCTGGAC CTGCATTACC GCGGGCGTGA CCGTGAGCGC GAGCCTGTGCCCGACCACCA AATGCACCAG CCGCTGC 414 Plantaricin Class IIa KYYGNGLSCLactobacillus 415 AAATATTATG C19 SKKGCTVN plantarum GCAACGGCCT WGQAFSCGGAGCTGCAGC VNRVATAG AAAAAAGGCT HGK GCACCGTGAA CTGGGGCCAG GCGTTTAGCTGCGGCGTGAA CCGCGTGGCG ACCGCGGGCC ATGGCAAA 416 Acidocin Class IIbGNPKVAHCA Lactobacillus 417 GGCAACCCGA J1132 β SQIGRSTAW acidophilusAAGTGGCGCA GAVSGA TTGCGCGAGC CAGATTGGCC GCAGCACCGC GTGGGGCGCG GTGAGCGGCGCG 418 factor Unclassified WLPPAGLLG Enterococcus 419 TGGCTGCCGC withanti- RCGRWFRP faecalis CGGCGGGCCT Candida WLLWLQSG GCTGGGCCGC activityAQYKWLGN TGCGGCCGCT LFGLGPK GGTTTCGCCC GTGGCTGCTG TGGCTGCAGA GCGGCGCGCAGTATAAATGG CTGGGCAACC TGTTTGGCCT GGGCCCGAAA 420 Ava_1098 UnclassifiedNLDQWLTE Anabaena 421 TAATTTAGATC (putative QVHEFQDM variabilisAGTGGTTAAC heterocyst YLEPQAISN ATCC 29413 AGAACAAGTT differentiationQDITFKLSDL CATGAGTTTC protein) DFIHN AAGATATGTA CTTGGAACCA CAAGCAATATCCAATCAAGA CATTACCTTCA AACTATCTGA CCTAGATTTTA TTCATAATTGA 422 alr2818Unclassified NLDQWLTE Nostoc sp 423 AATTTAGATC (putative QVHEFQDM 7120AATGGTTAAC heterocyst YLEPQAISN AGAACAAGTT differentiation QDITFKLSDLCATGAGTTTC protein) DFIHN AAGATATGTA CTTGGAACCA CAAGCAATAT CCAATCAAGACATTACCTTCA AACTGTCAGA CCTAGATTTTA TTCATAATTGA 424 Aazo_0724Unclassified HREKKSA Nostoc 425 CACAGAGAGA (putative azollae 0708AAAAATCAGC heterocyst ATAG differentiation protein) 426 AM1_4010Unclassified TSNNWLAK Acaryochloris 427 ACAAGCAATA (putative NYLSMWNKmarina ACTGGCTAGC heterocyst KSSNPNL MBIC11017 CAAAAACTATdifferentiation CTTTCTATGTG protein) GAATAAAAAG AGCAGTAATC CAAACCTTTAG428 PCC8801_3266 Unclassified FRYFWW Cyanothece 429 TTTAGATATTT(putative PCC 8801 TTGGTGGTAA heterocyst differentiation protein) 430Cyan8802_2855 Unclassified FRYFWW Cyanothece 431 TTTAGATATTT (putativePCC 8802 TTGGTGGTAA heterocyst differentiation protein) 432 PCC7424_3517Unclassified CGEKWRIFS Cyanothece 433 TGTGGAGAAA PCC 7424 AATGGAGAATTTTTAGC 434 cce_2677 Unclassified FRLQLWQF Cyanothece 435 TTTCGCTTACA(putative ATCC 51142 ACTGTGGCAA HetP TTT protein) 436 CY0110_11572Unclassified LGCNQSSIW Cyanothece 437 CTAGGATGTA (putative SIFFWNHCCY0110 ACCAGAGCAG heterocyst TATCTGGTCA differentiation ATTTTTTTCTGprotein) GAATCATTAA 438 MC7420_4637 Unclassified YNLQGLPAI Microcoleus439 TATAACCTAC ESEDCIPDSV chthonoplastes AGGGGTTGCC APSDDWFSG PCC 7420AGCAATTGAG VSSLFNRLT TCAGAAGACT GLG GTATCCCAGA TTCTGTAGCG CCTTCGGATGATTGGTTTTCA GGCGTATCGT CTCTGTTTAAC CGCTTGACTG GGTTGGGTTAG 440 asr1611Unclassified WMAIRRILR Nostoc sp 441 TGGATGGCGA (putative CHPFHPGGY 7120TTCGCCGCATT DUF37 DPVPELGEH TTGCGTTGTCA family CCHHDSGNKG TCCATTCCACCprotein) CAGGGGGTTA TGATCCTGTA CCAGAGTTGG GTGAGCATTG TTGTCATCATGATAGCGGGAA TAAGGGGTGA 442 Ava_4222 Unclassified WMGIRRILR Anabaena 443TGGATGGGGA (putative CHPFHPGGY variabilis TTCGCCGCATT DUF37 DPVPEVGEHATCC 29413 TTGCGTTGTCA family CCHHDSGK TCCATTCCACC protein) CAGGCGGTTATGATCCTGTA CCAGAGGTGG GTGAGCATTG TTGTCATCATG ATAGCGGGAA GTAG 444N9414_07129 Unclassified WMATRRILR Nodularia 445 TGGATGGCGA (putativeCHPFHPGGY spumigena CTCGGCGGAT DUF37 DPVPEVKHN CCY9414 TTTGCGTTGTCfamily CCDQHLSDS ATCCCTTCCAT protein) GKQTTEDHH CCTGGTGGAT KGSATGATCCAGT TCCAGAGGTA AAACACAATT GCTGCGATCA GCATCTGTCC GATTCTGGGAAACAGACCAC AGAAGACCAT CACAAAGGCT CGTAG 446 Aazo_0083 UnclassifiedWMATLRILC Nostoc 447 TGGATGGCAA (putative HPFHPGGYD azollae 0708CTTTGCGGATT DUF37 PVPGLAEKS TTACGCTGTC family CCDHHD ATCCTTTCCATprotein) CCTGGTGGTT ATGATCCTGT ACCAGGACTA GCGGAAAAAT CCTGTTGTGACCATCATGATT GA 448 S7335_3409 Unclassified WLTAKRFCR Synechococcus 449TGGCTAACAG (putative CHPLHPGGY PCC 7335 CCAAGCGCTT DUF37 DPVPEKKSVLTTGTCGCTGTC family ATCCGCTTCAT protein) CCTGGCGGGT ATGATCCGGT ACCGGAGAAGAAATCGGTAC TCTAA 450 P9303_21151 Unclassified WLTLRRLSR Prochlorococcus451 TGGCTCACCC (putative CHPFTPCGC marinus TGCGGCGCCT DUF37 DPVPD MIT9303 GTCTCGTTGCC family ATCCTTTTACC protein) CCCTGTGGTT GCGACCCGGTGCCTGATTAA

As used herein “bacteriocin polynucleotide” refers to a polynucleotideencoding a bacteriocin. In some embodiments, the host cell comprises atleast one bacteriocin.

Bacteriocin Immunity Modulators

Exemplary bacteriocin immunity modulators are shown in Table 2. Whilethe immunity modulators in Table 2 are naturally-occurring, the skilledartisan will appreciate that variants of the immunity modulators ofTable 2, naturally-occurring immunity modulators other than the immunitymodulators of Table 2, or synthetic immunity modulators can be usedaccording to some embodiments herein.

In some embodiments, a particular immunity modulator or particularcombination of immunity modulators confers immunity to a particularbacteriocin, particular class or category of bacteriocins, or particularcombination of bacteriocins. Exemplary bacteriocins to which immunitymodulators can confer immunity are identified in Table 2. While Table 2identifies an “organism of origin” for exemplary immunity modulators,these immunity modulators can readily be expressed in othernaturally-occurring, genetically modified, or synthetic microorganismsto provide a desired bacteriocin immunity activity in accordance withsome embodiments herein. As such, as used herein “immunity modulator”refers not only to structures expressly provided herein, but also tostructure that have substantially the same effect as the “immunitymodulator” structures described herein, including fully syntheticimmunity modulators, and immunity modulators that provide immunity tobacteriocins that are functionally equivalent to the bacteriocinsdisclosed herein.

Exemplary polynucleotide sequences encoding the polypeptides of Table 2are indicated in Table 2. The skilled artisan will readily understandthat the genetic code is degenerate, and moreover, codon usage can varybased on the particular organism in which the gene product is beingexpressed, and as such, a particular polypeptide can be encoded by morethan one polynucleotide. In some embodiments, a polynucleotide encodinga bacteriocin immunity modulator is selected based on the codon usage ofthe organism expressing the bacteriocin immunity modulator. In someembodiments, a polynucleotide encoding a bacteriocin immunity modulatoris codon optimized based on the particular organism expressing thebacteriocin immunity modulator. A vast range of functional immunitymodulators can incorporate features of immunity modulators disclosedherein, thus providing for a vast degree of identity to the immunitymodulators in Table 2. In some embodiments, an immunity modulator has atleast about 50% identity, for example, at least about 50%, 51%, 52%,53%, 54%, 55%, 56%, 57%, 58%, 59%, 60%, 61%, 62%, 63%, 64%, 65%, 66%,67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%,81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%,95%, 96%, 97%, 98%, 99%, or 100% identity to any one of the polypeptidesof Table 2.

TABLE 2 Exemplary bacteriocin immunity modulators Poly- Poly- peptidenucleotide SEQ Polypeptide Organism SEQ ID NO: Name Sequence of originID NO: Polynucleotide Sequence 452 Microcin MSYKKLY Escherichia 453ATGAGTTATAAAAAAC H47 QLTAIFSLP coli TGTACCAATTGACGGCT immunity LTILLVSLSATATTTAGTTTACCTCT modulator SLRIVGEG TACTATCTTATTGGTTT MchI NSYVDVFLCACTTTCATCCCTTCGG SFIIFLGFIE ATTGTTGGCGAAGGGA LIHGIRKILATTCTTATGTTGACGTT VWSGWKN TTTCTAAGCTTTATAAT GS ATTTCTTGGTTTTATTGAGCTGATTCATGGGATT CGAAAGATTTTGGTCTG GTCAGGCTGGAAAAAC GGAAGTTAA 454Colicin-E3 MGLKLDLT Escherichia 455 ATGGGACTTAAATTGG immunity WFDKSTEDcoli ATTTAACTTGGTTTGAT modulator FKGEEYSK AAAAGTACAGAAGATT (Colicin-E3DFGDDGSV TTAAGGGTGAGGAGTA chain B) MESLGVPF TTCAAAAGATTTTGGAG (ImmE3)KDNVNNG ATGACGGTTCAGTTATG (Microcin- CFDVIAEW GAAAGTCTAGGTGTGC E3VPLLQPYF CTTTTAAGGATAATGTT immunity NHQIDISD AATAACGGTTGCTTTGAmodulator) NEYFVSFD TGTTATAGCTGAATGG YRDGDW GTACCTTTGCTACAACCATACTTTAATCATCAAA TTGATATTTCCGATAAT GAGTATTTTGTTTCGTT TGATTATCGTGATGGTGATTGGTGA 456 Colicin-E1 MSLRYYIK Escherichia 457 ATGAGCTTAAGATACTAimmunity NILFGLYC coli CATAAAAAATATTTTAT modulator TLIYIYLITTTGGCCTGTACTGCACA (ImmE1) KNSEGYYF CTTATATATATATACCT (Microcin- LVSDKMLTATAACAAAAAACAGC E1 YAIVISTIL GAAGGGTATTATTTCCT immunity CPYSKYAITGTGTCAGATAAGATG modulator) EYIAFNFIK CTATATGCAATAGTGAT KDFFERRKAAGCACTATTCTATGTC NLNNAPVA CATATTCAAAATATGCT KLNLFMLY ATTGAATACATAGCTTTNLLCLVLA TAACTTCATAAAGAAA IPFGLLGLF GATTTTTTCGAAAGAAG ISIKNNAAAAAACCTAAATAAC GCCCCCGTAGCAAAATT AAACCTATTTATGCTAT ATAATCTACTTTGTTTGGTCCTAGCAATCCCATT TGGATTGCTAGGACTTT TTATATCAATAAAGAAT AATTAA 458 CloacinMGLKLHIH Escherichia 459 ATGGGGCTTAAATTAC immunity WFDKKTEE coliATATTCATTGGTTTGAT modulator FKGGEYSK AAGAAAACCGAAGAGT DFGDDGSVTTAAAGGCGGTGAATA IESLGMPL CTCAAAAGACTTCGGT KDNINNG GATGATGGTTCTGTCATWFDVEKP TGAAAGTCTGGGGATG WVSILQPH CCTTTAAAGGATAATAT FKNVIDISKTAATAATGGTTGGTTTG FDYFVSFV ATGTTGAAAAACCATG YRDGNW GGTTTCGATATTACAGCCACACTTTAAAAATGTA ATCGATATTAGTAAATT TGATTACTTTGTATCCT TTGTTTACCGGGATGGTAACTGGTAA 460 Colicin-E2 MELKHSIS Escherichia 461 ATGGAACTGAAACATAimmunity DYTEAEFL coli GTATTAGTGATTATACC modulator EFVKKICRGAGGCTGAATTTCTGG (ImmE2) AEGATEED AGTTTGTAAAAAAAAT (Microcin- DNKLVREFATGTAGAGCTGAAGGT E2 ERLTEHPD GCTACTGAAGAGGATG immunity GSDLIYYPACAATAAATTAGTGAG modulator) RDDREDSP AGAGTTTGAGCGATTA EGIVKEIKEACTGAGCACCCAGATG WRAANGK GTTCAGATCTGATTTAT SGFKQG TATCCTCGCGATGACAGGGAAGATAGTCCTGAA GGGATTGTCAAGGAAA TTAAAGAATGGCGAGC TGCTAACGGTAAGTCAGGATTTAAACAGGGCT GA 462 Colicin-A MMNEHSID Citrobacter 463ATGATGAATGAACACT immunity TDNRKAN freundii CAATAGATACGGACAA modulatorNALYLFIII CAGAAAGGCCAATAAC (Microcin- GLIPLLCIF GCATTGTATTTATTTATA immunity VVYYKTPD AATAATCGGATTAATAC modulator) ALLLRKIACATTATTGTGCATTTTT TSTENLPSI GTTGTTTACTACAAAAC TSSYNPLM GCCAGACGCTTTACTTTTKVMDIYC TACGTAAAATTGCTACA KTAPFLALI AGCACTGAGAATCTCCC LYILTFKIRGTCAATAACATCCTCCT KLINNTDR ACAACCCATTAATGACA NTVLRSCL AAGGTTATGGATATTTALSPLVYAA TTGTAAAACAGCGCCTT IVYLFCFR TCCTTGCCTTAATACTA NFELTTAGTACATCCTAACCTTTAA RPVRLMAT AATCAGAAAATTAATC NDATLLLF AACAACACCGACAGGAYIGLYSIIFF ACACTGTACTTAGATCT TTYITLFTP TGTTTATTAAGTCCATT VTAFKLLKGGTCTATGCAGCAATTG KRQ TTTATCTATTCTGCTTC CGAAATTTTGAGTTAACAACAGCCGGAAGGCCT GTCAGATTAATGGCCA CCAATGACGCAACACT ATTGTTATTTTATATTGGTCTGTACTCAATAATT TTCTTTACAACCTATAT CACGCTATTCACACCAG TCACTGCATTTAAATTATTAAAAAAAAGGCAGT AA 464 Colicin-Ia MNRKYYF Escherichia 465ATGAACAGAAAATATT immunity NNMWWG coli ATTTTAATAATATGTGG modulatorWVTGGYM TGGGGATGGGTGACGG LYMSWDY GGGGATATATGCTGTA EFKYRLLFTATGTCATGGGATTATG WCISLCGM AGTTTAAATACAGATTA VLYPVAK CTGTTCTGGTGTATTTCWYIEDTAL TCTCTGCGGAATGGTTT KFTRPDFW TGTATCCGGTTGCAAAA NSGFFADTTGGTATATTGAAGATAC PGKMGLLA AGCTCTAAAATTTACCC VYTGTVFI GGCCTGATTTCTGGAACLSLPLSMIY AGCGGTTTTTTTGCTGA ILSVIIKRLS TACACCTGGAAAAATG VRGGGTTGCTTGCGGTTTA TACGGGTACTGTTTTCA TATTATCTCTTCCGTTA AGTATGATATATATTCTTTCTGTTATTATAAAAA GGCTGTCTGTAAGATAG 466 Colicin-Ib MKLDISVK Escherichia467 ATGAAACTGGATATATC immunity YLLKSLIPI coli TGTAAAGTATTTACTGAmodulator LIILTVFYL AAAGCCTGATACCAAT GWKDNQE CCTCATTATTCTTACAG NARMFYAFTTTTTTATCTGGGATGG IGCIISAITF AAAGATAACCAGGAAA PFSMRIIQKATGCAAGAATGTTTTAT MVIRFTGK GCGTTCATCGGATGCAT EFWQKDFF TATCAGTGCCATTACTTTNPVGGSL TTCCTTTTTCAATGAGG TAIFELFCF ATAATACAGAAAATGG VISVPVVAITAATAAGGTTTACAGG YLIFILCKA GAAAGAATTCTGGCAA LSGK AAAGACTTCTTTACAAATCCAGTTGGCGGAAGC TTAACTGCAATATTTGA ATTATTCTGTTTCGTTA TATCAGTTCCTGTGGTTGCCATTTACTTAATTTT TATACTCTGCAAAGCCC TTTCAGGAAAATGA 468 Colicin-NMHNTLLEK Escherichia 469 ATGCACAATACACTCCT immunity IIAYLSLPG coliCGAAAAAATCATCGCA modulator FHSLNNPP TACCTATCCCTACCAGG (Microcin-LSEAFNLY ATTTCATTCATTAAACA N immunity VHTAPLAA ACCCGCCCCTAAGCGAmodulator) TSLFIFTHK AGCATTCAATCTCTATG ELELKPKS TTCATACAGCCCCTTTASPLRALKIL GCTGCAACCAGCTTATT TPFTILYIS CATATTCACACACAAAG MIYCFLLTAATTAGAGTTAAAACC DTELTLSS AAAGTCGTCACCTCTGC KTFVLIVK GGGCACTAAAGATATTKRSVFVFF AACTCCTTTCACTATTC LYNTIYWD TTTATATATCCATGATA IYIHIFVLLTACTGTTTCTTGCTAAC VPYRNI TGACACAGAACTAACC TTGTCATCAAAAACATTTGTATTAATAGTCAAAA AACGATCTGTTTTTGTC TTTTTTCTATATAACAC TATATATTGGGATATATATATTCACATATTTGTA CTTTTGGTTCCTTATAG GAACATATAA 470 Colicin-E8 MELKNSISEscherichia 471 ATGGAACTGAAAAACA immunity DYTETEFK coliGCATTAGTGATTACACT modulator KIIEDIINCE GAAACTGAATTCAAAA (ImmE8) GDEKKQDAAATTATTGAAGACATC (Microcin- DNLEHFIS ATCAATTGTGAAGGTG E8 VTEHPSGSATGAAAAAAAACAGGA immunity DLIYYPEG TGATAACCTCGAGCATT modulator) NNDGSPEATTATAAGTGTTACTGAG VIKEIKEW CATCCTAGTGGTTCTGA RAANGKSG TCTGATTTATTACCCAGFKQG AAGGTAATAATGATGG TAGCCCTGAAGCTGTTA TTAAAGAGATTAAAGAATGGCGAGCTGCTAAC GGTAAGTCAGGATTTA AACAGGGCTGA 472 Lactococcin-A MKKKQIEFLactococcus 473 ATGAAAAAAAAACAAA immunity ENELRSML lactisTAGAATTTGAAAACGA modulator ATALEKDI subsp. GCTAAGAAGTATGTTG SQEERNALlactis GCTACCGCCCTTGAAAA NIAEKALD (Streptococcus AGACATTAGTCAAGAGNSEYLPKII lactis) GAAAGAAATGCTCTGA LNLRKALT ATATTGCAGAAAAGGC PLAINRTLGCTTGACAATTCTGAAT NHDLSELY ATTTACCAAAAATTATT KFITSSKAS TTAAACCTCAGAAAAGNKNLGGG CCCTAACTCCATTAGCT LIMSWGRLF ATAAATCGAACACTTAA CCATGATTTATCTGAACTGTATAAATTCATTACA AGTTCCAAAGCATCAA ACAAAAATTTAGGTGG TGGTTTAATTATGTCGTGGGGACGACTATTCTAA 474 Lactococcin-A MKKKQIEF Lactococcus 475ATGAAAAAAAAACAAA immunity ENELRSML lactis TAGAATTTGAAAACGA modulatorATALEKDI subsp. GCTAAGAAGTATGTTG SQEERNAL cremoris GCTACCGCCCTTGAAAANIAEKALD (Streptococcus AGACATTAGTCAAGAG NSEYLPKII cremoris)GAAAGAAATGCTCTGA LNLRKALT ATATTGCAGAAAAGGC PLAINRTL GCTTGACAATTCTGAATNHDLSELY ATTTACCAAAAATTATT KFITSSKAS TTAAACCTCAGAAAAG NKNLGGGCCCTAACTCCATTAGCT LIMSWGRLF ATAAATCGAACACTTAA CCATGATTTATCTGAACTGTATAAATTCATTACA AGTTCCAAAGCATCAA ACAAAAATTTAGGTGG TGGTTTAATTATGTCGTGGGGACGACTATTCTAA 476 Colicin-D MNKMAMI Escherichia 477 ATGATCGATTTGGCGAimmunity DLAKLFLA coli AATTATTTTTAGCTTCG modulator SKITAIEFSAAAATTACAGTGATTG (Microcin- ERICVERR AGTTTTCAGAGCGAATT D immunityRLYGVKDL TGTGTTGAACGGAGAA modulator) SPNILNCG GATTGTATGGTGTTAAG EELFMAAEGATTTGTCTCCGAATAT RFEPDADR ATTAAATTGTGGGGAA ANYEIDDN GAGTTGTCTATGGCTGCGLKVEVRS TGAGCGATTTGAGCCT ILEKFKL GATGCAGATAGGGCTA ATTATGAAATTGATGATAATGGACTTAAGGTCG AGGTCCGATCTATCTTG GAAAAACTTAAATCAT AA 478 Colicin-E5MKLSPKAA Escherichia 479 ATGAAGTTATCACCAA immunity IEVCNEAA coliAAGCTGCAATAGAAGT modulator KKGLWILG TTGTAATGAAGCAGCG (ImmE5) IDGGHWLNAAAAAAGGCTTATGGA (Microcin- PGFRIDSSA TTTTGGGCATTGATGGT E5 SWTYDMPGGGCATTGGCTGAATC immunity EEYKSKIPE CTGGATTCAGGATAGA modulator)NNRLAIENI TAGTTCAGCATCATGGA KDDIENGY CATATGATATGCCGGA TAFIITLKMGAATACAAATCAAAAA TCCCTGAAAATAATAG ATTGGCTATTGAAAATA TTAAAGATGATATTGAGAATGGATACACTGCTT TCATTATCACGTTAA 480 Colicin-E6 MGLKLHIN Escherichia481 ATGGGGCTTAAATTAC immunity WFDKRTEE coli ATATTAATTGGTTTGAT modulatorFKGGEYSK AAGACGACCGAGGAAT (ImmE6) DFGDDGSV TTAAAGGTGGTGAGTA (Microcin-IERLGMPF TTCAAAAGATTTTGGAG E6 KDNINNG ATGATGGCTCGGTCATT immunityWFDVIAEW GAACGTCTTGGAATGC modulator) VPLLQPYF CTTTAAAAGATAATATC NHQIDISDAATAATGGTTGGTTTGA NEYFVSFD TGTTATAGCTGAATGG YRDGDW GTACCTTTGCTACAACCATACTTTAATCATCAAA TTGATATTTCCGATAAT GAGTATTTTGTTTCGTT TGATTATCGTGATGGTGATTGGTGA 482 Colicin-E8 MELKKSIG Escherichia 483 GTGGAGCTAAAGAAAAimmunity DYTETEFK coli GTATTGGTGATTACACT modulator KIIENIINCEGAAACCGAATTCAAAA in ColE6 GDEKKQD AAATTATTGAAAACATC (E8Imm[E6]) DNLEHFISATCAATTGTGAAGGTG VTEHPSGS ATGAAAAAAAACAGGA DLIYYPEG TGATAACCTCGAGCATTNNDGSPEA TTATAAGTGTTACTGAG VIKEIKEW CATCCTAGTGGTTCTGA RAANGKSGTCTGATTTATTACCCAG FKQG AAGGTAATAATGATGG TAGCCCTGAAGCTGTTATTAAAGAGATTAAAGA ATGGCGAGCTGCTAAC GGTAAGTCAGGATTTA AACAGGGCTGA 484Colicin-E9 MELKHSIS Escherichia 485 ATGGAACTGAAGCATA immunity DYTEAEFLcoli GCATTAGTGATTATACA modulator QLVTTICN GAAGCTGAATTTTTACA (ImmE9)ADTSSEEE ACTTGTAACAACAATTT (Microcin- LVKLVTHF GTAATGCGAACACTTCC E9EEMTEHPS AGTGAAGAAGAACTGG immunity GSDLIYYP TTAAATTGGTTACACAC modulator)KEGDDDSP TTTGAGGAAATGACTG SGIVNTVK AGCACCCTAGTGGTAG QWRAANGTGATTTAATATATTACC KSGFKQG CAAAAGAAGGTGATGA TGACTCACCTTCAGGTATTGTAAACACAGTAAA ACAATGGCGAGCCGCT AACGGTAAGTCAGGAT TTAAACAGGGCTAA 486Colicin-M MLTLYGYI Escherichia 487 ATGAAAGTAATTAGCA immunity RNVFLYRcoli TGAAATTTATTTTTATT modulator MNDRSCG TTAACGATTATTGCTCT (Microcin-MDFMKVISM TGCTGCTGTTTTTTTCT immunity KFIFILTIIA GGTCTGAAGATAAAGGmodulator) LAAVFFWS TCCGGCATGCTATCAGG EDKGPACY TCAGCGATGAACAGGC QVSDEQARCAGAACGTTTGTAAAA TFVKNDYL AATGATTACCTGCAAA QRMKRWD GAATGAAACGCTGGGANDVQLLGT CAACGATGTACAACTTC EIPKITWEK TTGGTACAGAAATCCC IERSLTDVEGAAAATTACATGGGAA DEKTLLVP AAGATTGAGAGAAGTT FKAEGPDG TAACAGATGTTGAAGAKRMYYGM TGAAAAAACACTTCTTG YHCEEGY TCCCATTTAAAGCTGAA VEYAKDGGCCCGGACGGTAAGA GAATGTATTATGGCATG TACCATTGTGAGGAGG GATATGTTGAATATGCGAATGACTAA 488 Colicin-B MTSNKDK Escherichia 489 ATGACCAGCAATAAAGimmunity NKKANEIL coli ATAAGAACAAGAAAGC modulator YAFSIIGIIPAAACGAAATATTATAT (Microcin- LMAILILRI GCATTTTCCATAATCGG B immunityNDPYSQVL GATTATTCCATTAATGG modulator) YYLYNKV CTATATTAATACTTCGAAFLPSITSL ATAAATGATCCATATTC HDPVMTTL TCAAGTGCTGTACTACT MSNYNKTTATATAATAAGGTGGC APVMGILV ATTTCTCCCTTCTATTA FLCTYKTR CATCATTGCATGATCCCEIIKPVTRK GTCATGACAACACTTAT LVVQSCFW GTCAAACTACAACAAG GPVFYAILIACAGCGCCAGTTATGG YITLFYNLE GTATTCTCGTTTTTCTT LTTAGGFF TGCACATATAAGACAAKLLSHNVI GAGAAATCATAAAGCC TLFILYCSI AGTAACAAGAAAACTT YFTVLTMTGTTGTGCAATCCTGTTT YAILLMPL CTGGGGGCCCGTTTTTT LVIKYFKG ATGCCATTCTGATTTATRQ ATCACACTGTTCTATAA TCTGGAACTAACAACA GCAGGTGGTTTTTTTAAATTATTATCTCATAATG TCATCACTCTGTTTATT TTATATTGCTCCATTTA CTTTACTGTTTTAACCATGACATATGCGATTTTA CTGATGCCATTACTTGT CATTAAATATTTTAAAG GGAGGCAGTAA 490Colicin-V MDRKRTK Escherichia 491 ATGGATAGAAAAAGAA immunity LELLFAFIIcoli CAAAATTAGAGTTGTTA modulator NATAIYIAL TTTGCATTTATAATAAA (Microcin-AIYDCVFR TGCCACCGCAATATATA V immunity GKDFLSMH TTGCATTAGCTATATATmodulator) TFCFSALM GATTGTGTTTTTAGAGG SAICYFVG AAAGGACTTTTTATCCADNYYSISD TGCATACATTTTGCTTC KIKRRSYE TCTGCATTAATGTCTGC NSDSKAATATGTTACTTTGTTG GTGATAATTATTATTCA ATATCCGATAAGATAA AAAGGAGATCATATGAGAACTCTGACTCTAAAT GA 492 Colicin- MSLRYYIK Shigella 493ATGAGTTTAAGATACTA E1* NILFGLYC sonnei CATAAAAAATATTTTGT immunityALIYIYLIT TTGGCCTATACTGCGCA modulator KNNEGYYF CTTATATATATATACCT (ImmE1)LASDKMLY TATAACAAAAAACAAC (Microcin- AIVISTILCP GAAGGGTATTATTTCCT E1*YSKYAIEHI AGCGTCAGATAAGATG immunity FFKFIKKDF CTATACGCAATAGTGATmodulator) FRKRKNLN AAGCACTATTCTATGCC KCPRGKIK CATATTCAAAATATGCTPYLCVYNL ATTGAACACATATTTTT LCLVLAIPF TAAGTTCATAAAGAAA GLLGLVYIGATTTTTTCAGAAAAAG NKE AAAAAACCTAAATAAA TGCCCCCGTGGCAAAATTAAACCGTATTTATGC GTATACAATCTACTTTG TTTGGTCCTAGCAATCC CATTTGGATTGCTAGGACTTGTTTATATCAATAA AGAATAA 494 Colicin-E1 MSLRYYIK Escherichia 495ATGAGCTTAAGATACTA immunity NILFGLYC coli CATAAAAAATATTTTAT modulatorTLIYIYLIT TTGGCCTGTACTGCACA (ImmE1) KNSEEYYF CTTATATATATATACCT(Microcin- LVTDKML TATAACAAAAAACAGC E1 YAIVISTIL GAAGAGTATTATTTCCTimmunity CPYSKYAI TGTGACAGATAAGATG modulator) EHIAFNFIKCTATATGCAATAGTGAT KHFFERRK AAGCACTATTCTATGTC NLNNAPVA CATATTCAAAATATGCTKLNLFMLY ATTGAACACATAGCTTT NLLCLVLA TAACTTCATAAAGAAAC IPFGLLGLFATTTTTTCGAAAGAAGA ISIKNN AAAAACCTAAATAACG CCCCCGTAGCAAAATTAAACCTATTTATGCTATA TAATCTACTTTGTTTGG TCCTAGCAATCCCATTT GGATTGCTAGGACTTTTTATATCAATAAAGAATA ATTAA 496 Probable MRKNNILL Leuconostoc 497TTGAGAAAAAATAACA leucocin-A DDAKIYTN gelidum TTTTATTGGACGATGCT immunityKLYLLLID AAAATATACACGAACA modulator RKDDAGY AACTCTATTTGCTATTA GDICDVLFATCGATAGAAAAGATG QVSKKLDS ACGCTGGGTATGGAGA TKNVEALI TATTTGTGATGTTTTGTNRLVNYIRI TTCAGGTATCCAAAAA TASTNRIKF ATTAGATAGCACAAAA SKDEEAVIIAATGTAGAAGCATTGA ELGVIGQK TTAACCGATTGGTCAAT AGLNGQY TATATACGAATTACCGCMADFSDKS TTCAACAAACAGAATTA QFYSIFER AGTTTTCAAAAGATGA AGAGGCTGTAATTATAGAACTTGGTGTAATTG GTCAGAAGGCTGGATT AAACGGCCAATACATG GCTGATTTTTCTGACAAATCTCAGTTTTATAGTA TCTTTGAAAGATAA 498 Lactococcin-B MKKKVDT Lactococcus499 ATGAAAAAAAAAGTTG immunity EKQITSWA lactis ATACAGAAAAACAAAT modulatorSDLASKNE subsp. TACTTCTTGGGCATCTG TKVQEKLI cremoris ACTTAGCTTCCAAAAATLSSYIQDIE (Streptococcus GAAACAAAGGTTCAAG NHVYFPKA cremoris)AAAAATTAATACTGTCT MISLEKKL TCTTATATTCAGGACAT RDQNNICA CGAAAACCATGTTTACTLSKEVNQF TTCCAAAAGCAATGATT YFKVVEVN TCTTTAGAAAAAAAATT QRKSWMVACGAGACCAAAATAAT GLIV ATTTGCGCTTTATCAAA AGAAGTCAATCAGTTTTATTTTAAAGTTGTTGAA GTAAATCAAAGAAAAT CCTGGATGGTAGGTTTG ATAGTTTAA 500Pediocin MNKTKSE Pediococcus 501 ATGAATAAGACTAAGT PA-1 HIKQQALDacidilactici CGGAACATATTAAACA immunity LFTRLQFLL ACAAGCTTTGGACTTATmodulator QKHDTIEP TTACTAGGCTACAGTTT (Pediocin YQYVLDIL TTACTACAGAAGCACGACH ETGISKTK ATACTATCGAACCTTAC immunity HNQQTPER CAGTACGTTTTAGATATmodulator) QARVVYN TCTGGAGACTGGTATCA KIASQALV GTAAAACTAAACATAA DKLHFTAECCAGCAAACGCCTGAA ENKVLAAI CGACAAGCTCGTGTAG NELAHSQK TCTACAACAAGATTGCCGWGEFNM AGCCAAGCGTTAGTAG LDTTNTWP ATAAGTTACATTTTACT SQ GCCGAAGAAAACAAAGTTCTAGCAGCCATCAAT GAATTGGCGCATTCTCA AAAAGGGTGGGGCGAG TTTAACATGCTAGATACTACCAATACGTGGCCTA GCCAATAG 502 Putative MIKDEKIN Carnobacterium 503ATGATAAAAGATGAAA carnobacteriocin- KIYALVKS maltaromaticumAAATAAATAAAATCTAT BM1 ALDNTDV (Carnobacterium GCTTTAGTTAAGAGCGC immunityKNDKKLSL piscicola) ACTTGATAATACGGAT modulator LLMRIQET GTTAAGAATGATAAAASINGELFY AACTTTCTTTACTTCTT DYKKELQP ATGAGAATACAAGAAA AISMYSIQCATCAATTAATGGAGA HNFRVPDD ACTATTTTACGATTATA LVKLLALV AAAAAGAATTACAGCCQTPKAWS AGCTATTAGTATGTACT GF CTATTCAACATAACTTT CGGGTTCCTGACGATCTAGTAAAACTGTTAGCAT TAGTTCAAACACCTAAA GCTTGGTCAGGGTTTTAA 504 PutativeMDIKSQTL Carnobacterium 505 ATGGATATAAAGTCTCA carnobacteriocin- YLNLSEAYmaltaromaticum AACATTATATTTGAATC B2 KDPEVKAN (CarnobacteriumTAAGCGAGGCATATAA immunity EFLSKLVV piscicola) AGACCCTGAAGTAAAA modulatorQCAGKLTA GCTAATGAATTCTTATC (Carnocin- SNSENSYIE AAAATTAGTTGTACAAT CP52VISLLSRGI GTGCTGGGAAATTAAC immunity SSYYLSHK AGCTTCAAACAGTGAG modulator)RIIPSSMLTI AACAGTTATATTGAAGT YTQIQKDI AATATCATTGCTATCTA KNGNIDTEGGGGTATTTCTAGTTAT KLRKYEIA TATTTATCCCATAAACG KGLMSVPY TATAATTCCTTCAAGTAIYF TGTTAACTATATATACT CAAATACAAAAGGATA TAAAAAACGGGAATAT TGACACCGAAAAATTAAGGAAATATGAGATAG CAAAAGGATTAATGTC CGTTCCTTATATATATT TCTAA 506 NisinMRRYLILI Lactococcus 507 ATGAGAAGATATTTAAT immunity VALIGITGL lactisACTTATTGTGGCCTTAA modulator SGCYQTSH subsp. TAGGGATAACAGGTTT KKVRFDEGlactis ATCAGGGTGTTATCAA SYTNFIYD (Streptococcus ACAAGTCATAAAAAGGNKSYFVTD lactis) TGAGGTTTGACGAAGG KEIPQENV AAGTTATACTAATTTTA NNSKVKFYTTTATGATAATAAATCG KLLIVDMK TATTTCGTAACTGATAA SEKLLSSSN GGAGATTCCTCAGGAGKNSVTLVL AACGTTAACAATTCCAA NNIYEASD AGTAAAATTTTATAAGC KSLCMGINTGTTGATTGTTGACATG DRYYKILP AAAAGTGAGAAACTTT ESDKGAVK TATCAAGTAGCAACAAALRLQNFD AAATAGTGTGACTTTGG VTSDISDD TCTTAAATAATATTTAT NFVIDKNDGAGGCTTCTGACAAGT SRKIDYMG CGCTATGTATGGGTATT NIYSISDTT AACGACAGATACTATAVSDEELGE AGATACTTCCAGAAAG YQDVLAE TGATAAGGGGGCGGTC VRVFDSVSAAAGCTTTGAGATTACA GKSIPRSE AAACTTTGATGTGACAA WGRIDKD GCGATATTTCTGATGATGSNSKQSR AATTTTGTTATTGATAA TEWDYGEI AAATGATTCACGAAAA HSIRGKSLTATTGACTATATGGGAA EAFAVEIN ATATTTACAGTATATCG DDFKLATK GACACCACCGTATCTGAVGN TGAAGAATTGGGAGAA TATCAGGATGTTTTAGC TGAAGTACGTGTGTTTGATTCAGTTAGTGGCAA AAGTATCCCGAGGTCT GAATGGGGGAGAATTG ATAAGGATGGTTCAAATTCCAAACAGAGTAGG ACGGAATGGGATTATG GCGAAATCCATTCTATT AGAGGAAAATCTCTTACTGAAGCATTTGCCGTT GAGATAAATGATGATT TTAAGCTTGCAACGAA GGTAGGAAACTAG 508Trifolitoxin MNDEICLT Rhizobium 509 ATGAATGATGAGATTT immunity GGGRTTVTleguminosarum GCCTGACAGGTGGCGG modulator RRGGVVY bv. ACGAACGACTGTCACGREGGPWSS trifolii CGGCGCGGCGGAGTCG TVISLLRHL TGTATCGCGAAGGCGG EASGFAEACCCGTGGTCATCAACCG PSVVGTGF TCATTTCGCTCCTGCGG DERGRETL CATCTGGAAGCCTCTGGSFIEGEFVH CTTCGCTGAAGCTCCTT PGPWSEEA CCGTTGTCGGCACCGGT FPQFGMMLTTCGATGAGCGCGGCC RRLHDATA GGGAGACATTATCGTTT SFKPPENS ATCGAGGGTGAGTTTGMWRDWFG TTCACCCAGGCCCTTGG RNLGEGQH TCGGAGGAGGCTTTTCC VIGHCDTGGCAATTTGGAATGATGT PWNIVCRS TGCGGCGACTGCACGA GLPVGLID TGCCACCGCCTCGTTCAWEVAGPV AACCTCCCGAAAACTC RADIELAQ GATGTGGCGCGATTGG ACWLNAQTTCGGGCGTAACCTCG LYDDDIAE GTGAGGGTCAACACGT RVGLGSVT AATAGGACACTGCGACMRAHQVR ACAGGCCCATGGAACA LLLDGYGL TTGTTTGCCGGTCAGGA SRKQRGGFTTGCCTGTCGGGTTGAT VDKLITFA AGATTGGGAGGTGGCT VHDAAEQ GGGCCTGTCAGGGCGGAKEAAVTP ATATCGAATTGGCCCA ESNDAEPL GGCTTGTTGGCTGAATG WAIAWRTCCCAGCTCTACGATGAC RSASWML GACATTGCGGAGAGGG HHRQTLEA TCGGATTAGGCTCTGTGALA ACCATGAGAGCGCATC AAGTTCGCCTGCTGCTT GACGGCTATGGTCTGTCTCGGAAGCAACGCGGC GGCTTCGTCGACAAGCT AATCACGTTCGCAGTTC ACGATGCGGCCGAGCAGGCGAAAGAGGCGGCT GTCACGCCAGAGTCGA ACGATGCGGAACCGCT ATGGGCAATTGCCTGGCGCACTAGAAGTGCCT CCTGGATGCTCCATCAT CGGCAAACACTGGAAG CAGCGCTGGCATAG 510Antilisterial MNNIIPIMS Bacillus 511 ATGAATAACATAATCCC bacteriocinLLFKQLYS subtilis TATCATGTCTTTGCTGT subtilosin RQGKKDAI (strain 168)TCAAACAGCTTTACAGC biosynthesis RIAAGLVIL CGGCAAGGGAAAAAGG proteinAVFEIGLIR ACGCCATCCGCATTGCC AlbD QAGIDESV GCAGGCCTTGTCATTCT LRKTYIILAGGCCGTGTTTGAAATC LLLMNTY GGGCTGATCCGCCAGG MVFLSVTS CCGGCATTGATGAATCQWKESYM GGTGTTGCGCAAAACG KLSCLLPIS TATATCATACTCGCGCT SRSFWLAQTCTTTTGATGAACACAT SVVLFVDT ATATGGTGTTTCTTTCC CLRRTLFFF GTGACATCACAATGGAILPLFLFGN AGGAATCTTATATGAA GTLSGAQT GCTGAGCTGCCTGCTGC LFWLGRFSCGATTTCTTCACGGAGC FFTVYSIIF TTTTGGCTCGCCCAGAG GVVLSNHF TGTCGTTTTGTTTGTCGVKKKNLM ATACCTGTTTGAGAAG FLLHAAIFA AACTTTATTCTTTTTTA CVCISAALTTTTACCGCTGTTCTTA MPAATIPL TTTGGAAACGGAACGC CAVHILWA TGTCAGGGGCGCAAACVVIDFPVFL ATTGTTTTGGCTCGGCA QAPPQQGK GGTTTTCGTTTTTTACC MHSFMRRSGTTTACTCCATTATTTT EFSFYKRE CGGAGTTGTGCTAAGC WNRFISSK AACCACTTCGTCAAAAAAMLLNYA GAAGAACTTGATGTTTC VMAVFSGF TGCTGCATGCGGCGAT FSFQMMNTATTCGCCTGTGTATGTA GIFNQQVI TCAGCGCCGCTTTGATG YIVISALLL CCGGCCGCCACGATTCCICSPIALLY GCTTTGCGCGGTTCATA SIEKNDRM TCCTGTGGGCGGTGGT LLITLPIKRCATTGACTTTCCTGTCT KTMFWAK TTCTGCAGGCGCCTCCG YRFYSGLL CAGCAGGGCAAGATGCAGGFLLVV ATTCATTTATGCGGCGA MIVGFISGR TCTGAATTTTCGTTTTA SISVLTFLQCAAAAGAGAATGGAAC CIELLLAG CGATTTATCTCTTCTAA AYIRLTAD AGCGATGCTGTTAAATTEKRPSFSW ACGCGGTAATGGCGGT QTEQQLWS ATTCAGCGGCTTCTTTT GFSKYRSYCGTTCCAGATGATGAA LFCLPLFLA CACCGGCATCTTCAATC ILAGTAVS AGCAAGTGATTTATATCLAVIPIAGL GTGATTTCCGCGCTTTT VIVYYLQK GCTCATCTGCTCGCCGA QDGGFFDTTCGCCCTTTTGTATTCG SKRERLGS ATTGAAAAAAATGACC GGATGCTGCTCATCACGCTTCCGATCAAGCGAA AAACGATGTTTTGGGC GAAATATCGCTTTTATT CAGGCCTATTGGCAGGCGGATTTCTCCTTGTCG TGATGATTGTGGGTTTCA 512 Putative MSILDIHD Bacillus 513GCATTTTGGATATACAC ABC VSVWYER subtilis GATGTATCCGTTTGGTA transporterDNVILEQV (strain 168) TGAACGGGACAACGTC ATP- DLHLEKGA ATCTTAGAGCACGTGGbinding VYGLLGV ACTTACACTTAGAAAAA protein NGAGKTTL GGCGCCGTTTACGGATTAlbC INTLTGVN GCTTGGGGTAAACGGT (Antilisterial RNFSGRFT GCCGGCAAAACAACACbacteriocin LCGIEAEA TGATCAATACGCTGACA subtilosin GMPQKTSDGGAGTGAACCGCAATT biosynthesis QLKTHRYF ACAGCGGGGGCTTTAC protein AADYPLLFGCTGTGCGGCATTGAA AlbC) TEITAKDY GCTGAGGCCGGCATGC VSFVHSLYCGCAGAAAACATCAGA QKDFSEQQ TCAACTGAAGATTCACC FASLAEAF GTTACTTCGCCGCTGATHFSKYINR TATCCGCTGCTGTTTAC RISELSLGN AGAAATTACGGCGAAG RQKVVLMGACTATGTGTCTTTCGT TGLLLRAP CCATTCGCTTTATCAAA LFILDEPLV AGGATTTTTCAGAGCGGLDVESIE ACAGTTTGCCAGTTTGG VFYQKMR CTGAGGCCTTTCATTTT EYCEAGGTTCAAAATACATCAACA ILFSSHLLD GGAGAATCTCGGAGCT VVQRFCDY GTCCTTGGGGAACAGGAAILHNKQ CAAAAGGTTGTGTTGAT IQKVIPIGE GACAGGATTATTGCTGC ETDLRREFGGGCTCCCCTGTTTATT FEVIGHE TTGGATGAGCCGCTCGT CGGTTTGGATGTGGAATCAATAGAGGTCTTTTA TCAGAAAATGCGGGAG TACTGTGAGGAAGGCG GAACCATTTTGTTTTCTTCCCATCTGCTCGATGT CGTGCAGAGATTTTGTG ATTTTGCGGCCATTCTG CACAACAAACAGATCCAAAAGGTCATTCCGATT GGGGAGGAGACCGATC TGCGGCGGGAATTTTTT GAGGTTATCGGCCATGAATAA 514 Antilisterial MSPAQRRI Bacillus 515 TTGTCACCAGCACAAAbacteriocin LLYILSFIF subtilis GAAGAATTTTACTGTAT subtilosin VIGAVVYF(strain 168) ATCCTTTCATTTATCTT biosynthesis VKSDYLFT TGTCATCGGCGCAGTCprotein LIFIAIAILF GTCTATTTTGTCAAAAG AlbB GMRARKA CGATTATCTGTTTACGC DSRTGATTTTCATTGCCATT GCCATTCTGTTCGGGAT GCGCGCGCGGAAGGCT GACTCGCGATGA 516Colicin-E7 MELKNSIS Escherichia 517 ATGGAACTGAAAAATA immunity DYTEAEFVcoli GTATTAGTGATTACACA modulator QLLKEIEK GAGGCTGAGTTTGTTCA (ImmE7)ENVAATD ACTTCTTAAGGAAATTG (Microcin- DVLDVLLE AAAAAGAGAATGTTGC E7HFVKITEH TGCAACTGATGATGTGT immunity PDGTDLIY TAGATGTGTTACTCGAAmodulator) YPSDNRDD CACTTTGTAAAAATTAC SPEGIVKEI TGAGCATCCAGATGGA KEWRAANACGGATCTGATTTATTA GKPGFKQG TCCTAGTGATAATAGA GACGATAGCCCCGAAGGGATTGTCAAGGAAAT TAAAGAATGGCGAGCT GCTAACGGTAAGCCAG GATTTAAACAGGGCTGA 518Pyocin-S1 MKSKISEY Pseudomonas 519 ATGAAGTCCAAGATTTC immunity TEKEFLEFaeruginosa CGAATATACGGAAAAA modulator VEDIYTNN GAGTTTCTTGAGTTTGTKKKFPTEE TGAAGACATATACACA SHIQAVLE AACAATAAGAAAAAGT FKKLTEHPTCCCTACCGAGGAGTCT SGSDLLYY CATATTCAAGCCGTGCT PNENREDS TGAATTTAAAAAACTAAPAGVVKEV CGGAACACCCAAGCGG KEWRASK CTCAGACCTTCTTTACT GLPGFKAGACCCCAACGAAAATAG AGAAGATAGCCCAGCT GGAGTTGTAAAGGAAG TTAAAGAATGGCGTGCTTCCAAGGGGCTTCCTG GCTTTAAGGCCGGTTAG 520 Pyocin-S2 MKSKISEY Pseudomonas521 ATGAAGTCCAAGATTTC immunity TEKEFLEF aeruginosa CGAATATACGGAAAAAmodulator VKDIYTNN (strain GAGTTTCTTGAGTTTGT KKKFPTEE ATCCTAAAGACATATACACA SHIQAVLE 15692/ AACAATAAGAAAAAGT FKKLTEHP PAO1/1C/TCCCTACCGAGGAGTCT SGSDLLYY PRS 101/ CATATTCAAGCCGTGCT PNENREDS LMGTGAATTTAAAAAACTAA PAGVVKEV 12228) CGGAACACCCAAGCGG KEWRASKCTCAGACCTTCTTTACT GLPGFKAG ACCCCAACGAAAATAG AGAAGATAGCCCAGCTGGAGTTGTAAAGGAAG TTAAAGAATGGCGTGC TTCCAAGGGGCTTCCTG GCTTTAAGGCCGGTTAG522 Hiracin- MDFTKEEK Enterococcus 523 ATGGATTTTACTAAAGA JM79 LLNAISKVhirae AGAAAAACTTTTAAAT immunity YNEATIDD GCAATTAGTAAAGTAT factorYPDLKEKL ACAATGAAGCAACTAT FLYSKEISE AGATGACTATCCTGACT GKSVGEVSTAAAAGAAAAGCTCTTT MKLSSFLG CTTTATTCTAAAGAAAT RYILKHKF CAGTGAGGGAAAAAGTGLPKSLIEL GTTGGTGAAGTTAGTAT QEIVSKES GAAATTAAGTAGTTTTC QVYRGWATTGGAAGATATATTTTA SIGIWS AAACATAAATTTGGATT ACCTAAATCTTTAATAGAATTACAAGAAATTGTT AGTAAGGAATCTCAAG TATATAGAGGATGGGC TTCTATTGGTATTTGGAGTTAA 524 Probable MKKKYRY Leuconostoc 525 TTGAAAAAAAAGTATCmesentericin- LEDSKNYT mesenteroides GGTATTTAGAAGATAG Y105 STLYSLLVCAAAAATTACACTAGTA immunity DNVDKPG CACTCTATTCTCTGTTA modulator YSDICDVLGTTGATAATGTTGACAA LQVSKKLD ACCTGGATACTCAGATA NTQSVEAL TTTGCGATGTTTTGCTTINRLVNYIR CAAGTTTCTAAGAAGTT ITASTYKIIF GGATAATACTCAAAGT SKKEEELIIGTTGAAGCGCTAATTA KLGVIGQK ATCGATTGGTTAATTAT AGLNGQY ATTCGTATTACTGCTTCMADFSDKS AACATACAAAATTATTT QFYSVFDQ TTTCAAAAAAAGAAGA GGAATTGATTATAAAACTTGGTGTTATTGGACA AAAAGCTGGACTTAAT GGTCAGTATATGGCTG ATTTTTCAGACAAGTCTCAGTTTTACAGCGTTTT CGATCAGTAA 526 Microcin- MSFLNFAF Escherichia 527ATGAGTTTTCTTAATTT 24 SPVFFSIMA coli TGCATTTTCTCCTGTAT immunity CYFIVWRNTCTTCTCCATTATGGCG modulator KRNEFVCN TGTTATTTCATTGTATG RLLSIIIISFLGAGAAATAAACGAAAC ICFIYPWLN GAATTTGTCTGCAATAG YKIEVKYY ATTGCTATCAATTATAAIFEQFYLFC TAATATCTTTTTTGATA FLSSLVAV TGCTTCATATATCCATG VINLIVYFIGCTAAATTACAAAATC LYRRCI GAAGTTAAATATTATAT ATTTGAACAGTTTTATCTTTTTTGTTTTTTATCGT CACTCGTGGCTGTTGTA ATAAACCTAATTGTATA CTTTATATTATACAGGAGATGTATATGA 528 Colicin-K MHLKYYL Escherichia 529 ATGCATTTAAAATACTAimmunity HNLPESLIP coli CCTACATAATTTACCTG modulator WILILIFNDAATCACTTATACCATGG NDNTPLLFI ATTCTTATTTTAATATT FISSIHVLL TAACGACAATGATAACYPYSKLTIS ACTCCTTTGTTATTTAT RYIKENTK ATTTATATCATCAATAC LKKEPWYLATGTATTGCTATATCCA CKLSALFY TACTCTAAATTAACCAT LLMAIPVG ATCTAGATATATCAAAGLPSFIYYTL AAAATACAAAGTTAAA KRN AAAAGAACCCTGGTAC TTATGCAAGTTATCTGCATTGTTTTATTTATTAA TGGCAATCCCAGTAGG ATTGCCAAGTTTCATAT ATTACACTCTAAAGAGAAATTAA 530 Microcin MMIQSHPL Escherichia 531 ATGATGATACAATCTCA C7 self-LAAPLAVG coli TCCACTACTGGCCGCTC immunity DTIGFFSSS CCCTGGCAGTAGGAGAmodulator APATVTAK TACAATTGGTTTCTTTT MccF NRFFRGVE CATCATCTGCTCCGGCAFLQRKGFK ACAGTTACTGCAAAAA LVSGKLTG ATCGTTTTTTTCGGGGA KTDFYRSGGTTGAGTTTCTTCAGAG TIKERAQE AAAGGGATTTAAGCTG FNELVYNP GTATCAGGGAAGCTTADITCIMSTI CCGGTAAAACAGATTTT GGDNSNSL TATCGTTCAGGTACTAT LPFLDYDATAAAGAAAGAGCTCAA IIANPKIIIG GAATTTAATGAGTTAGT YSDTTALL CTACAATCCTGATATTAAGIYAKTG CCTGTATAATGTCAACG LITFYGPAL ATCGGTGGAGATAACA IPSFGEHPPGTAATTCACTACTACCG LVDITYESF TTTCTGGACTATGATGC IKILTRKQSTATCATTGCAAACCCCA GIYTYTLP AAATTATCATAGGTTAC EKWSDESI TCAGATACAACTGCTTTNWNENKIL ATTAGCAGGAATATAT RPKKLYKN GCAAAAACAGGGTTAA NCAFYGSGTAACATTCTATGGACCA KVEGRVIG GCTCTTATTCCTTCGTT GNLNTLTG TGGTGAACATCCACCTCIWGSEWM TTGTGGATATAACATAT PEILNGDIL GAATCATTTATTAAAAT FIEDSRKSIACTAACAAGAAAACAA ATIERLFS TCAGGAATATATACCTA MLKLNRVF CACATTACCTGAAAAGTDKVSAIILG GGAGTGATGAGAGCAT KHELFDCA AAACTGGAATGAAAAC GSKRRPYEAAGATATTAAGGCCTA VLTEVLDG AGAAGCTATATAAAAA KQIPVLDG CAACTGTGCCTTTTATGFDCSHTHP GTTCCGGAAAAGTTGA MLTLPLGV GGGGCGTGTAATTGGA KLAIDFDNGGAAATCTAAATACTTT KNISITEQY GACAGGTATATGGGGG LSTEK AGTGAATGGATGCCTGAAATTCTTAATGGAGAT ATATTGTTTATTGAGGA CAGTCGGAAAAGCATT GCAACAATTGAACGATTATTCTCTATGCTAAAG CTTAATCGCGTGTTTGA TAAAGTTAGTGCAATA ATACTCGGGAAACATGAGCTTTTTGATTGTGCA GGAAGTAAACGCAGAC CATATGAAGTATTAACA GAGGTATTAGATGGGAAACAGATTCCTGTACTG GATGGATTTGATTGTTC ACATACACATCCAATGC TAACTCTTCCACTTGGTGTAAAATTAGCTATTGA CTTTGACAACAAAAATA TAT 532 Sakacin-A MKADYKKILactobacillus 533 GGCAGATTATAAAAAA immunity NSILTYTST sakeiATAAATTCAATACTAAC factor ALKNPKIIK TTACACATCTACTGCTT DKDLVVLLTAAAAAACCCTAAAATT TIIQEEAKQ ATAAAAGATAAAGATT NRIFYDYK TAGTAGTCCTTCTAACTRKFRPAVT ATTATTCAAGAAGAAG RFTIDNNFE CCAAACAAAATAGAAT IPDCLVKLCTTTTATGATTATAAAA LSAVETPK GAAAATTTCGTCCAGC AWSGFS GGTTACTCGCTTTACAATTGATAATAATTTTGAG ATTCCTGATTGTTTGGT TAAACTACTGTCAGCTG TTGAAACACCTAAGGCGTGGTCTGGATTTAGTT AG 534 Colicin-E5 MKLSPKAA Escherichia 535TGAAGTTATCACCAAA immunity IEVCNEAA coli AGCTGCAATAGAAGTT modulatorKKGLWILG TGTAATGAAGCAGCGA in ColE9 IDGGHWLN AAAAAGGCTTATGGAT (E5Imm[E9])PGFRIDSSA TTTGGGCATTGATGGTG SWTYDMP GGCATTGGCTGAATCCT EEYKSKTPGGATTCAGGATAGATA ENNRLAIE GTTCAGCATCATGGAC NIKDDIEN ATATGATATGCCGGAGGYTAFIITL GAATACAAATCAAAAA KM CCCCTGAAAATAATAG ATTGGCTATTGAAAATATTAAAGATGATATTGA GAATGGATACACTGCTT TCATTATCACGTTAAAG ATGTAA 536Antilisterial MNNIFPIM Bacillus 537 TTGGGGAGGAGACCGA bacteriocinSLLFKQLY subtilis TCTGCGGCGGGAATTTT subtilosin SRQGKKDATTGAGGTTATCGGCCAT biosynthesis IRIAAGLVI GAATAACATATTCCCCA proteinLAVFEIGLI TCATGTCGTTGCTGTTC AlbD RQAGIDES AAACAGCTGTACAGCC VLGKTYIILGGCAAGGGAAAAAGGA ALLLMNTY CGCTATCCGCATTGCTG MVFLSVTS CAGGGCTTGTGATTCTCQWKESYM GCCGTGTTTGAAATCG KLSCLLPIS GGCTGATCCGACAAGC SRSFWLAQCGGCATTGACGAATCG SVVLFVDT GTGTTGGGAAAAACGT CLRRTLFFF ATATCATATTGGCGCTTILPLFLFGN CTCTTAATGAACACGTA GTLSGAQT TATGGTGTTTCTTTCCG LFWLGRFSTGACATCACAATGGAA FFTVYSILF GGAATCTTATATGAAG GVMLSNHF CTGAGCTGTCTGCTGCCVKKKNSM GATTTCATCACGGAGCT FLLHAAVF TTTGGCTCGCCCAGAGT AFVCLSAAGTCGTTCTGTTTGTCGA FMPAVTIP TACCTGTTTGAGAAGA LCAVHML ACGTTATTCTTTTTTATWAVIIDFP TTTACCGCTGTTCTTAT VFLQAPPH TTGGAAACGGAACGCT QSKMHFFGTCAGGGGCGCAAACA MRRSEFSF TTGTTTTGGCTTGGCAG YKREWNR ATTTTCGTTTTTTACCGFISSKAMLL TTTACTCGATTCTATTC NYVVMAA GGAGTTATGCTAAGCA FSGFFSFQACCATTTCGTCAAAAAG MMNTGIFN AAGAACTCGATGTTTCT QQVIYIVIS GCTGCATGCGGCGGTAALLLICSPI TTCGCCTTTGTATGCCT ALLYSIEK CAGTGCCGCTTTTATGC NDRMLLITCGGCCGTCACGATCCC LPIKRRTM GCTATGCGCGGTTCACA FWAKYRF TGCTATGGGCGGTGATYSGLLAGG CATTGACTTTCCGGTCT FLLVAIIVG TTCTGCAGGCGCCTCCG FISGRPISACATCAGAGCAAGATGC LTFVQCME ATTTTTTTATGCGGCGA LLLAGAFIR TCTGAATTTTCGTTTTALTADEKRP CAAAAGAGAATGGAAC SFGWQTEQ CGATTTATTTCTTCTAA QLWSGFSKAGCGATGCTGTTAAATT YRSYLFCL ACGTGGTGATGGCGGC PLFLATLA GTTCAGCGGATTCTTTTGTAVSLAV CGTTCCAGATGATGAA IPIAALIIVY CACTGGCATCTTCAATC YLQKQDGAGCAAGTGATTTATATT GFFDTSKR GTGATTTCCGCTCTATT ERIGS GCTGATTTGCTCGCCGATCGCCCTTTTGTACTCT ATTGAAAAAAACGATC GCATGCTGCTCATCACG CTTCCAATTAAAAGAAGAACGATGTTTTGGGC GAAATATCGCTTTTATT CAG 538 Microcin- MERKQKN Escherichia539 ATGGAAAGAAAACAGA J25 export SLFNYIYSL coli AAAACTCATTATTTAAT ATP-MDVRGKF TATATTTATTCATTAAT binding/permease LFFSMLFIT GGATGTAAGAGGTAAAprotein SLSSIIISISP TTTTTATTCTTTTCCAT McjD LILAKITDL GTTATTCATTACATCAT(Microcin- LSGSLSNFS TATCATCGATAATCATA J25 YEYLVLLA TCTATTTCACCATTGATimmunity CLYMFCVI TCTTGCAAAGATTACAG modulator) SNKASVFLATTTACTGTCTGGCTCA (Microcin- FMILQSSLR TTGTCAAATTTTAGTTA J25 INMQKKMTGAATATCTGGTTTTAC secretion SLKYLREL TTGCCTGTTTATACATG ATP- YNENITNLTTTTGCGTTATATCTAA binding SKNNAGYT TAAAGCAAGTGTTTTTT protein TQSLNQASTATTTATGATACTGCAA McjD) NDIYILVR AGTAGTCTACGTATTAA NVSQNILSCATGCAGAAAAAAATG PVIQLISTI TCGCTAAAGTATTTGAG VVVLSTKD AGAATTGTATAACGAAWFSAGVFF AATATAACTAACTTGAG LYILVFVIF TAAAAATAATGCTGGA NTRLTGSLTATACAACGCAAAGTCT ASLRKHSM TAACCAGGCTTCAAATG DITLNSYSL ACATTTATATTCTTGTGLSDTVDN AGAAATGTTTCCCAGA MIAAKKNN ATATCCTGTCACCTGTT ALRLISERYATACAACTTATTTCCAC EDALTQEN TATTGTTGTTGTTTTAT NAQKKYW CTACGAAGGACTGGTTTLLSSKVLL TCTGCCGGTGTGTTTTT LNSLLAVIL TCTCTATATTCTGGTAT FGSVFIYNITTGTAATTTTTAATACC LGVLNGV AGACTGACTGGCAGTTT VSIGHFIMI AGCGTCTCTCAGAAAATSYIILLST CACAGCATGGATATCA PVENIGAL CTCTTAACTCTTATAGT LSEIRQSMCTGTTATCTGATACTGT SSLAGFIQR TGATAACATGATAGCA HAENKATS GCTAAAAAGAATAATGPSIPFLNME CATTAAGACTTATTTCT RKLNLSIRE GAACGTTATGAAGATG LSFSYSDDCTCTCACTCAGGAAAAC KKILNSVS AATGCTCAGAAAAAAT LDLFTGKM ACTGGTTACTCAGTTCTYSLTGPSG AAAGTTCTTTTATTGAA SGKSTLVK CTCTTTACTTGCTGTAA IISGYYKNTATTATTTGGTTCTGTA YFGDIYLN TTCATATATAATATTTT DISLRNISD AGGTGTGCTGAATGGTEDLNDAIY GTAGTTAGTATCGGCCA YLTQDDYI CTTCATTATGATTACAT FMDTLRFNCATATATCATTCTTCTT LRLANYDA TCAACGCCAGTGGAAA SENEIFKVL ATATAGGGGCATTGCTKLANLSVV AAGTGAGATCAGGCAG NNEPVSLD TCAATGTCTAGCCTGGC THLINRGNAGGTTTTATTCAACGTC NYSGGQK ATGCCGAGAATAAAGC QRISLARLF CACATCTCCTTCAALRKPAIIIID EATSALDY INESEILSSI RTHFPDALI INISHRINL LECSDCVY VLNEGNIVASGHFRDL MVSNEYIS GLASVTE 540 Microcin MTLLSFGF Klebsiella 541ATGACATTACTTTCATT E492 SPVFFSVM pneumoniae TGGATTTTCTCCTGTTT immunityAFCIISRSK TCTTTTCAGTCATGGCG modulator FYPQRTRN TTCTGTATCATTTCACGKVIVLILLT TAGTAAATTCTATCCGC FFICFLYPL AGAGAACGCGAAACAA TKVYLVGSAGTTATTGTTCTGATTT YGIFDKFY TACTAACTTTTTTTATT LFCFISTLI TGTTTTTTATATCCATTAIAINVVIL AACAAAAGTGTATCTG TINGAKNE GTGGGAAGTTACGGTA RNTATTTGACAAATTCTAC CTCTTTTGCTTTATTTC TACGTTAATTGCAATAG CAATTAACGTAGTGATACTTACAATAAATGGAG CTAAGAATGAGAGAAA TTAGPoison-Antidote Systems

It can be desirable to contain a particular microbial cell within adesired environment, for example by killing or arresting the growth ofthe microbial cell if it is no longer in the desired environment.Poison-antidote systems, which are distinct from bacteriocins, can beuseful for accomplishing such containment, or for other selective growthof microbial cells. Exemplary poison antidote systems are described inU.S. Pat. Nos. 5,910,438, 6,180,407, 7,176,029, and 7,183,097, each ofwhich is hereby incorporated by reference in its entirety. In someembodiments, a poison-antidote system comprises a cytotoxic (poison)polypeptide, and a corresponding antitoxin (antidote) polypeptide in asingle cell. As used herein, a “poison polynucleotide” refers to apolynucleotide encoding a poison polypeptide, and an “antidotepolynucleotide” refers to a polynucleotide encoding an antidotepolypeptide.

In some embodiments, the poison polypeptide is expressed constitutively,while the antidote polypeptide is only expressed under desiredconditions. In some embodiments, the poison polypeptide is onlyexpressed under undesired conditions, while the antidote polypeptide isonly expressed under desired conditions. For example, in someembodiments, a poison/antidote system is configured so that themicrobial cell survives under desired environmental conditions, but diesunder undesired environmental conditions. For example, in someembodiments, a poison antidote system is configured so that themicrobial cell is killed if it escapes from the environment in which itis being used in an industrial process. In other embodiments, a poisonantidote system is configured so that the microbial cell survives when avector (e.g. a plasmid) encoding an antidote polypeptide is present, butdies when the vector is absent. In some embodiments, the poisonpolypeptide is encoded by a poison polynucleotide in the host genome,while the antidote polypeptide is encoded by an antidote polynucleotideon a vector (such as a plasmid or extrachromosomal array or episome orminichromosome), and as such is only expressed when the vector ispresent in the host cell. In some embodiments, the poison polypeptide isencoded by a poison polynucleotide on a first vector, while the antidotepolypeptide is encoded by an antidote polynucleotide on a second vector,and as such is only expressed when the second vector is present. In someembodiments, the presence of the antidote polynucleotide (and thus thepresence of the antidote polypeptide) depends on the presence or absenceof a recombination event, for example the integration of apolynucleotide sequence encoding the antidote polynucleotide into thehost genome. It should be appreciated that in some embodiments in whichexpression of the antidote polypeptide depends on the presence orabsence of a vector or recombination event, the poison and antidotepolypeptide can each be expressed constitutively. Optionally, in someembodiments in which expression of the antidote polypeptide depends onthe presence or absence of a vector or a recombination event, expressionof the poison polypeptide and/or antidote polypeptide is conditional,for example so that the poison is only expressed in conditions in whichthe microbial cell is not desired, and/or the antidote polypeptide isonly expressed in conditions in which the microbial cell is desired.

Exemplary microbial toxin polypeptide/antitoxin polypeptide pairs (alsoreferred to as “poison/antidote” pairs) that can used in poison antidotesystems in conjunction with some embodiments herein include, but are notlimited to RelE/RelB, CcdB/CcdA, Kis/Kid, SoK/HoK, PasB (or PasC)/PasA,PemK/PemI, Doc/Phd, MazE/MazF and ParE/ParD. Without being limited byany particular theory, many poison polypeptides, for example RelE, arehighly conserved across Gram-positive and Gram-negative bacteria andArchae, and as such, can have cytotoxic activity in a broad range ofnaturally occurring, genetically modified, and fully synthetic microbialcells. Further, without being limited by any particular theory, it iscontemplated that an antidote polypeptide can generally inhibit theactivity of its poison polypeptide partner in a variety of hostenvironments, and as such, poison/antidote pairs such as those describedherein can readily be used in a broad range of naturally occurring,genetically modified, and fully synthetic microbial cells.

It is noted that a poison-antidote system is distinct from a bacteriocinsystem at least in that a poison-antidote system provides an endogenoussystem by which a microbial cell can kill or arrest itself, while abacteriocin system provides an exogenous system by which a microbialcell can kill or arrest other cells. It is further noted, however, that,while a poison-antidote system cannot be used to kill or arrest cellsother than the individual cell in which the poison is produced, in someembodiments, a poison-antidote system may be used along with abacteriocin system as described herein. For example, in some embodimentsa bacteriocin system as described herein may be used to kill or arrestthe growth of cells other than the bacteriocin producing cell in aculture while the poison-antidote system may be used to kill or arrestthe growth of the bacteriocin producing cell should it escape from itsdesired environment. A poison-antidote system may also be used to selectfor bacteriocin producing cells which have been genetically engineeredto express a molecule useful in an industrial process (an “industriallyuseful molecule”). For example, in some embodiments, expression of anantidote can be tied to expression of an industrially useful molecule orbacteriocin by placing polynucleotides encoding the bacteriocin and theindustrially useful molecule, or polynucleotides encoding thebacteriocin and antidote under the control of a single promoter.Accordingly, in some embodiments, a microbial cell encoding abacteriocin or bacteriocin immunity modulator further comprises a poisonantidote system. In some embodiments, the bacteriocin system is usefulfor regulating growth of the microbial cell or other microbial cellswithin a particular environment, while the poison-antidote system isuseful for containing the microbial cell within a particularenvironment.

Promoters

Promoters are well known in the art. A promoter can be used to drive thetranscription of one or more genes. In some embodiments, a promoterdrives expression of polynucleotide encoding a desired gene product asdescribed herein. In some embodiments, a promoter drives expression of abacteriocin polynucleotide as described herein. In some embodiments, apromoter drives expression of an immunity modulator polynucleotide asdescribed herein. In some embodiments, a promoter drives expression of abacteriocin nucleotide and an immunity modulator polynucleotide. In someembodiments, a promoter drives expression of polynucleotide encoding atleast one of a bacteriocin, immunity modulator, industrially usefulmolecule, poison molecule, or antidote molecule. Some promoters candrive transcription at all times (“constitutive promoters”). Somepromoters can drive transcription under only select circumstances(“conditional promoters”), for example depending on the presence orabsence of an environmental condition, chemical compound, gene product,stage of the cell cycle, or the like.

The skilled artisan will appreciate that depending on the desiredexpression activity, an appropriate promoter can be selected, and placedin cis with a sequence to be expressed. Exemplary promoters withexemplary activities are provided in Table 3.1-3.11 herein. The skilledartisan will appreciate that some promoters are compatible withparticular transcriptional machinery (e.g. RNA polymerases, generaltranscription factors, and the like). As such, while compatible“species” are identified for some promoters described herein, it iscontemplated that according to some embodiments herein, these promoterscan readily function in microorganisms other than the identifiedspecies, for example in species with compatible endogenoustranscriptional machinery, genetically modified species comprisingcompatible transcriptional machinery, or fully synthetic microbialorganisms comprising compatible transcriptional machinery.

The promoters of Tables 3.1-3.11 herein are publicly available from theBiobricks foundation. Per the Biobricks foundation, use of thesepromoters in accordance with BioBrick™ Public Agreement (BPA) isencouraged.

It should be appreciated that any of the “coding” polynucleotidesdescribed herein (for example a bacteriocin polynucleotide, immunitypolynucleotide, poison polynucleotide, antidote polynucleotide, orproduct polynucleotide) is generally amenable to being expressed underthe control of a desired promoter. In some embodiments, a single“coding” polynucleotide is under the control of a single promoter. Insome embodiments, two or more “coding” polynucleotides are under thecontrol of a single promoter, for example two, three, four, five, six,seven, eight, nine, or ten polynucleotides. As such, in someembodiments, a “cocktail” of different bacteriocins can be produced by asingle microbial organism. In some embodiments, a bacteriocinpolynucleotide is under the control of a promoter. In some embodiments,an immunity modulator is under the control of a promoter. In someembodiments, a polynucleotide encoding a desired gene product is underthe control of a promoter. In some embodiments, the bacteriocinpolynucleotide and the polynucleotide encoding a desired gene productare under the control of the same promoter. In some embodiments, abacteriocin polynucleotide and the polynucleotide encoding a desiredgene product are under the control of different promoters. In someembodiments, the immunity modulator polynucleotide and thepolynucleotide encoding a desired gene product are under the control ofthe same promoter. In some embodiments, the bacteriocin polynucleotideand the immunity modulator polynucleotide are under the control ofdifferent promoters.

Generally, translation initiation for a particular transcript isregulated by particular sequences at or 5′ of the 5′ end of the codingsequence of a transcript. For example, a coding sequence can begin witha start codon configured to pair with an initiator tRNA. Whilenaturally-occurring translation systems typically use Met (AUG) as astart codon, it will be readily appreciated that an initiator tRNA canbe engineered to bind to any desired triplet or triplets, andaccordingly, triplets other than AUG can also function as start codonsin certain embodiments. Additionally, sequences near the start codon canfacilitate ribosomal assembly, for example a Kozak sequence((gcc)gccRccAUGG, SEQ ID NO: 542, in which R represents “A” or “G”) orInternal Ribosome Entry Site (IRES) in typical eukaryotic translationalsystems, or a Shine-Delgarno sequence (GGAGGU, SEQ ID NO: 543) intypical prokaryotic translation systems. As such in some embodiments, atranscript comprising a “coding” polynucleotide sequence, for example abacteriocin polynucleotide or immunity modulator polynucleotide, orpolynucleotide encoding a desired industrial product, comprises anappropriate start codon and translational initiation sequence. In someembodiments, for example if two or more “coding” polynucleotidesequences are positioned in cis on a transcript, each polynucleotidesequence comprises an appropriate start codon and translationalinitiation sequence(s). In some embodiments, for example if two or more“coding” polynucleotide sequences are positioned in cis on a transcript,the two sequences are under control of a single translation initiationsequence, and either provide a single polypeptide that can function withboth encoded polypeptides in cis, or provide a means for separating twopolypeptides encoded in cis, for example a 2A sequence or the like. Insome embodiments, a translational intiator tRNA is regulatable, so as toregulate initiation of translation of a bacteriocin, immunity modulator,poison molecule, antidote molecule, or industrially useful molecule.

TABLE 3.1 Exemplary Metal-Sensitive Promoters SEQ ID NO: NameDescription Sequence 544 BBa_I721001 Lead Promotergaaaaccttgtcaatgaagagcgatctatg 545 BBa_I731004 FecA promoterttctcgttcgactcatagctgaacacaaca 546 BBa_I760005 Cu-sensitive promoteratgacaaaattgtcat 547 BBa_I765000 Fe promoteraccaatgctgggaacggccagggcacctaa 548 BBa_I765007 Fe and UV promotersctgaaagcgcataccgctatggagggggtt 549 BBa_J3902 PrFe (PI + PII rus operon)tagatatgcctgaaagcgcataccgctatg

TABLE 3.2 Exemplary Cell Signaling-Responsive Promoters SEQ ID NO: NameDescription Sequence 550 BBa_I1051 Lux cassette right promotertgttatagtcgaatacctctggcggtgata 551 BBa_I14015 P(Las) TetOttttggtacactccctatcagtgatagaga 552 BBa_I14016 P(Las) CIOctttttggtacactacctctggcggtgata 553 BBa_I14017 P(Rhl)tacgcaagaaaatggtttgttatagtcgaa 554 BBa_I739105 Double Promoter(LuxR/HSL, cgtgcgtgttgataacaccgtgcgtgttga positive/cI, negative) 555BBa_I746104 P2 promoter in agr operon agattgtactaaatcgtataatgacagtgafrom S. aureus 556 BBa_I751501 plux-cI hybrid promotergtgttgatgcttttatcaccgccagtggta 557 BBa_I751502 plux-lac hybrid promoteragtgtgtggaattgtgagcggataacaatt 558 BBa_I761011 CinR, CinL and glucoseacatcttaaaagttttagtatcatattcgt controlled promotor 559 BBa_J06403 RhIRpromoter repressible by tacgcaagaaaatggtttgttatagtcgaa CI 560BBa_J102001 Reverse Lux Promoter tcttgcgtaaacctgtacgatcctacaggt 561BBa_J64000 rhlI promoter atcctcctttagtcttccccctcatgtgtg 562 BBa_J64010lasI promoter taaaattatgaaatttgcataaattcttca 563 BBa_J64067 LuxR+ 3OC6HSL independent gtgttgactattttacctctggcggtgata R0065 564BBa_J64712 LasR/LasI Inducible & gaaatctggcagtttttggtacacgaaagcRHLR/RHLI repressible Promoter 565 BBa_K091107 pLux/cI Hybrid Promoteracaccgtgcgtgttgatatagtcgaataaa 566 BBa_K091117 pLas promoteraaaattatgaaatttgtataaattcttcag 567 BBa_K091143 pLas/cI Hybrid Promoterggttctttttggtacctctggcggtgataa 568 BBa_K091146 pLas/Lux Hybrid Promotertgtaggatcgtacaggtataaattcttcag 569 BBa_K091156 pLuxcaagaaaatggtttgttatagtcgaataaa 570 BBa_K091157 pLux/Las Hybrid Promoterctatctcatttgctagtatagtcgaataaa 571 BBa_K145150 Hybrid promoter: HSL-LuxRtagtttataatttaagtgttctttaatttc activated, P22 C2 repressed 572BBa_K266000 PAI + LasR -> LuxI (AI) caccttcgggtgggcctttctgcgtttata 573BBa_K266005 PAI + LasR -> LasI & aataactctgatagtgctagtgtagatctc AI+ LuxR --|LasI 574 BBa_K266006 PAI + LasR -> LasI + GFP &caccttcgggtgggcctttctgcgtttata AI + LuxR --|LasI + GFP 575 BBa_K266007Complex QS -> LuxI & LasI caccttcgggtgggcctttctgcgtttata circuit 576BBa_K658006 position 3 mutated promoter caagaaaatggtttgttatagtcgaataaalux pR-3 (luxR & HSL regulated) 577 BBa_K658007 position 5 mutatedpromoter caagaaaatggtttgttatagtcgaataaa lux pR-5 (luxR & HSL regulated)578 BBa_K658008 position 3&5 mutated caagaaaatggtttgttatagtcgaataaapromoter lux pR-3/5 (luxR & HSL regulated) 579 BBa_R0061 Promoter(HSL-mediated luxR ttgacacctgtaggatcgtacaggtataat repressor) 580BBa_R0062 Promoter (luxR & HSL caagaaaatggtttgttatagtcgaataaa regulated-- lux pR) 581 BBa_R0063 Promoter (luxR & HSLcacgcaaaacttgcgacaaacaataggtaa regulated -- lux pL) 582 BBa_R0071Promoter (Rh1R & C4-HSL gttagctttcgaattggctaaaaagtgttc regulated) 583BBa_R0078 Promoter (cinR and HSL ccattctgctttccacgaacttgaaaacgcregulated) 584 BBa_R0079 Promoter (LasR & PAIggccgcgggttctttttggtacacgaaagc regulated) 585 BBa_R1062 Promoter,Standard (luxR and aagaaaatggtttgttgatactcgaataaa HSL regulated -- luxpR)

TABLE 3.3 Exemplary Constitutive E. coli σ⁷⁰ Promoters SEQ ID NO: NameDescription Sequence 586 BBa_I14018 P(Bla)gtttatacataggcgagtactctgttatgg 587 BBa_I14033 P(Cat)agaggttccaactttcaccataatgaaaca 588 BBa_I14034 P(Kat)taaacaactaacggacaattctacctaaca 589 BBa_I732021 Template for BuildingPrimer acatcaagccaaattaaacaggattaacac Family Member 590 BBa_I742126Reverse lambda cI-regulated gaggtaaaatagtcaacacgcacggtgtta promoter 591BBa_J01006 Key Promoter absorbs 3 caggccggaataactccctataatgcgcca 592BBa_J23100 constitutive promoter family ggctagctcagtcctaggtacagtgctagcmember 593 BBa_J23101 constitutive promoter familyagctagctcagtcctaggtattatgctagc member 594 BBa_J23102 constitutivepromoter family agctagctcagtcctaggtactgtgctagc member 595 BBa_J23103constitutive promoter family agctagctcagtcctagggattatgctagc member 596BBa_J23104 constitutive promoter family agctagctcagtcctaggtattgtgctagcmember 597 BBa_J23105 constitutive promoter familyggctagctcagtcctaggtactatgctagc member 598 BBa_J23106 constitutivepromoter family ggctagctcagtcctaggtatagtgctagc member 599 BBa_J23107constitutive promoter family ggctagctcagccctaggtattatgctagc member 600BBa_J23108 constitutive promoter family agctagctcagtcctaggtataatgctagcmember 601 BBa_J23109 constitutive promoter familyagctagctcagtcctagggactgtgctagc member 602 BBa_J23110 constitutivepromoter family ggctagctcagtcctaggtacaatgctagc member 603 BBa_J23111constitutive promoter family ggctagctcagtcctaggtatagtgctagc member 604BBa_J23112 constitutive promoter family agctagctcagtcctagggattatgctagcmember 605 BBa_J23113 constitutive promoter familyggctagctcagtcctagggattatgctagc member 606 BBa_J23114 constitutivepromoter family ggctagctcagtcctaggtacaatgctagc member 607 BBa_J23115constitutive promoter family agctagctcagcccttggtacaatgctagc member 608BBa_J23116 constitutive promoter family agctagctcagtcctagggactatgctagcmember 609 BBa_J23117 constitutive promoter familyagctagctcagtcctagggattgtgctagc member 610 BBa_J23118 constitutivepromoter family ggctagctcagtcctaggtattgtgctagc member 611 BBa_J23119constitutive promoter family agctagctcagtcctaggtataatgctagc member 612BBa_J23150 1bp mutant from J23107 ggctagctcagtcctaggtattatgctagc 613BBa_J23151 1bp mutant from J23114 ggctagctcagtcctaggtacaatgctagc 614BBa_J44002 pBAD reverse aaagtgtgacgccgtgcaaataatcaatgt 615 BBa_J48104NikR promoter, a protein of gacgaatacttaaaatcgtcatacttattt the ribbonhelix-helix family of trancription factors that repress expre 616BBa_J54200 lacq_Promoter aaacctttcgcggtatggcatgatagcgcc 617 BBa_J56015lacIQ - promoter sequence tgatagcgcccggaagagagtcaattcagg 618 BBa_J64951E. Coli CreABCD phosphate ttatttaccgtgacgaactaattgctcgtg sensing operonpromoter 619 BBa_K088007 GlnRS promoter catacgccgttatacgttgtttacgctttg620 BBa_K119000 Constitutive weak promoter ofttatgcttccggctcgtatgttgtgtggac lacZ 621 BBa_K119001 Mutated LacZpromoter ttatgcttccggctcgtatggtgtgtggac 622 BBa_K137029 constitutivepromoter with atatatatatatatataatggaagcgtttt (TA)10 between −10 and −35elements 623 BBa_K137030 constitutive promoter withatatatatatatatataatggaagcgtttt (TA)9 between −10 and −35 elements 624BBa_K137031 constitutive promoter with ccccgaaagcttaagaatataattgtaagc(C)10 between −10 and −35 elements 625 BBa_K137032 constitutive promoterwith ccccgaaagcttaagaatataattgtaagc (C)12 between −10 and −35 elements626 BBa_K137085 optimized (TA) repeat tgacaatatatatatatatataatgctagcconstitutive promoter with 13 bp between −10 and −35 elements 627BBa_K137086 optimized (TA) repeat acaatatatatatatatatataatgctagcconstitutive promoter with 15 bp between −10 and −35 elements 628BBa_K137087 optimized (TA) repeat aatatatatatatatatatataatgctagcconstitutive promoter with 17 bp between −10 and −35 elements 629BBa_K137088 optimized (TA) repeat tatatatatatatatatatataatgctagcconstitutive promoter with 19 bp between −10 and −35 elements 630BBa_K137089 optimized (TA) repeat tatatatatatatatatatataatgctagcconstitutive promoter with 21 bp between −10 and −35 elements 631BBa_K137090 optimized (A) repeat aaaaaaaaaaaaaaaaaatataatgctagcconstitutive promoter with 17 bp between −10 and −35 elements 632BBa_K137091 optimized (A) repeat aaaaaaaaaaaaaaaaaatataatgctagcconstitutive promoter with 18 bp between −10 and −35 elements 633BBa_K256002 J23101:GFP caccttcgggtgggcctttctgcgtttata 634 BBa_K256018J23119:IFP caccttcgggtgggcctttctgcgtttata 635 BBa_K256020 J23119:HO1caccttcgggtgggcctttctgcgtttata 636 BBa_K256033 Infrared signal reportercaccttcgggtgggcctttctgcgtttata (J23119:IFP:J23119:HO1) 637 BBa_K292000Double terminator + ggctagctcagtcctaggtacagtgctagc constitutive promoter638 BBa_K292001 Double terminator + tgctagctactagagattaaagaggagaaaConstitutive promoter + Strong RBS 639 BBa_K418000 IPTG inducible Lacpromoter ttgtgagcggataacaagatactgagcaca cassette 640 BBa_K418002 IPTGinducible Lac promoter ttgtgagcggataacaagatactgagcaca cassette 641BBa_K418003 IPTG inducible Lac promoter ttgtgagcggataacaagatactgagcacacassette 642 BBa_M13101 M13K07 gene I promotercctgtttttatgttattctctctgtaaagg 643 BBa_M13102 M13K07 gene II promoteraaatatttgcttatacaatcttcctgtttt 644 BBa_M13103 M13K07 gene III promotergctgataaaccgatacaattaaaggctcct 645 BBa_M13104 M13K07 gene IV promoterctcttctcagcgtcttaatctaagctatcg 646 BBa_M13105 M13K07 gene V promoteratgagccagttcttaaaatcgcataaggta 647 BBa_M13106 M13K07 gene VI promoterctattgattgtgacaaaataaacttattcc 648 BBa_M13108 M13K07 gene VIII promotergtttcgcgcttggtataatcgctgggggtc 649 BBa_M13110 M13110ctttgcttctgactataatagtcagggtaa 650 BBa_M31519 Modified promoter sequenceof aaaccgatacaattaaaggctcctgctagc g3. 651 BBa_R1074 ConstitutivePromoter I caccacactgatagtgctagtgtagatcac 652 BBa_R1075 ConstitutivePromoter II gccggaataactccctataatgcgccacca 653 BBa_S03331 --SpecifyParts List-- ttgacaagcttttcctcagctccgtaaact

TABLE 3.4 Exemplary Constitutive E. coli σ^(s) Promoters SEQ ID NO: NameDescription Sequence 654 BBa_J45992 Full-length ggtttcaaaattgtgastationary phase tctatatttaacaa osmY promoter 655 BBa_J45993 Minimalstationary ggtttcaaaattgtga phase osmY promoter tctatatttaacaa

TABLE 3.5 Exemplary Constitutive E. coli σ³² Promoters SEQ ID NO: NameDescription Sequence 656 BBa_J45504 htpG Heat Shock tctattccaataaagaaatPromoter cttcctgcgtg

TABLE 3.6 Exemplary Constitutive B. subtilis σ^(A) Promoters SEQ ID NO:Name Description Sequence 657 BBa_K143012 Promoter veg a constitutiveaaaaatgggctcgtgttgtacaataaatgt promoter for B. subtilis 658 BBa_K143013Promoter 43 a constitutive aaaaaaagcgcgcgattatgtaaaatataa promoter forB. subtilis 659 BBa_K780003 Strong constitutive promoteraattgcagtaggcatgacaaaatggactca for Bacillus subtilis 660 BBa_K823000PliaG caagcttttcctttataatagaatgaatga 661 BBa_K823002 PlepAtctaagctagtgtattttgcgtttaatagt 662 BBa_K823003 Pvegaatgggctcgtgttgtacaataaatgtagt

TABLE 3.7 Exemplary Constitutive B. subtilis σ^(B) Promoters SEQ ID NO:Name Description Sequence 663 BBa_K143010 Promoter ctc atccttatcgttatggfor B. subtilis gtattgtttgtaat 664 BBa_K143011 Promoter gsiBtaaaagaattgtga for B. subtilis gcgggaatacaacaac 665 BBa_K143013 Promoter43 a aaaaaaagcgcgcg constitutive attatgtaaaatataa promoter for B.subtilis

TABLE 3.8 Exemplary Constitutive Promoters from miscellaneousprokaryotes SEQ ID NO: Name Description Sequence 666 a_K112706 Pspv2from tacaaaataattccc Salmonella ctgcaaacattatca 667 BBa_K112707 Pspvfrom tacaaaataattcc Salmonella cctgcaaacattatcg

TABLE 3.9 Exemplary Constitutive Promoters from bacteriophage T7 SEQ IDNO: Name Description Sequence 668 BBa_I712074 T7 promoter (strongagggaatacaagctacttgttctttttgca promoter from T7 bacteriophage) 669BBa_I719005 T7 Promoter taatacgactcactatagggaga 670 BBa_J34814 T7Promoter gaatttaatacgactcactatagggaga 671 BBa_J64997 T7 consensus −10and rest taatacgactcactatagg 672 BBa_K113010 overlapping T7 promotergagtcgtattaatacgactcactatagggg 673 BBa_K113011 more overlapping T7agtgagtcgtactacgactcactatagggg promoter 674 BBa_K113012 weakenoverlapping T7 gagtcgtattaatacgactctctatagggg promoter 675 BBa_R0085 T7Consensus Promoter taatacgactcactatagggaga Sequence 676 BBa_R0180 T7RNAP promoter ttatacgactcactatagggaga 677 BBa_R0181 T7 RNAP promotergaatacgactcactatagggaga 678 BBa_R0182 T7 RNAP promotertaatacgtctcactatagggaga 679 BBa_R0183 T7 RNAP promotertcatacgactcactatagggaga 680 BBa_Z0251 T7 strong promotertaatacgactcactatagggagaccacaac 681 BBa_Z0252 T7 weak binding andtaattgaactcactaaagggagaccacagc processivity 682 BBa_Z0253 T7 weakbinding promoter cgaagtaatacgactcactattagggaaga

TABLE 3.10 Exemplary Constitutive Promoters from yeast SEQ ID NO: NameDescription Sequence 683 BBa_I766555 pCyc (Medium) Promoteracaaacacaaatacacacactaaattaata 684 BBa_I766556 pAdh (Strong) Promoterccaagcatacaatcaactatctcatataca 685 BBa_I766557 pSte5 (Weak) Promotergatacaggatacagcggaaacaacttttaa 686 BBa_J63005 yeast ADH1 promotertttcaagctataccaagcatacaatcaact 687 BBa_K105027 cyc100 minimal promotercctttgcagcataaattactatacttctat 688 BBa_K105028 cyc70 minimal promotercctttgcagcataaattactatacttctat 689 BBa_K105029 cyc43 minimal promotercctttgcagcataaattactatacttctat 690 BBa_K105030 cyc28 minimal promotercctttgcagcataaattactatacttctat 691 BBa_K105031 cyc16 minimal promotercctttgcagcataaattactatacttctat 692 BBa_K122000 pPGK1ttatctactttttacaacaaatataaaaca 693 BBa_K124000 pCYC Yeast Promoteracaaacacaaatacacacactaaattaata 694 BBa_K124002 Yeast GPD (TDH3)gtttcgaataaacacacataaacaaacaaa Promoter 695 BBa_K319005 yeast mid-lengthADH1 ccaagcatacaatcaactatctcatataca promoter 696 BBa_M31201 Yeast CLB1promoter accatcaaaggaagctttaatcttctcata region, G2/M cell cycle specific

TABLE 3.11 Exemplary Constitutive Promoters from miscellaneouseukaryotes SEQ ID NO: Name Description Sequence 697 BBa_I712004 CMVpromoter agaacccactgcttactggct tatcgaaat 698 BBa_K076017 Ubc Promoterggccgtttttggcttttttgtt agacgaag

The above-referenced promoters are provided by way of non-limitingexample only. The skilled artisan will readily recognize that manyvariants of the above-referenced promoters, and many other promoters(including promoters isolated from naturally existing organisms,variations thereof, and fully synthetic promoters) can readily be usedin accordance with some embodiments herein.

Regulation of Gene Activity

Gene activity can be regulated to either increase or decrease activityof the gene product. In some embodiments, the gene product for whichactivity is regulated comprises a bacteriocin, immunity modulator,industrially useful molecule, poison molecule, or antidote molecule. Insome embodiments, two or more of such gene products are regulated undera single gene regulation system. In some embodiments, gene activity isregulated at the level of gene expression. In some embodiments, geneactivity is regulated at the transcriptional level, for example byactivating or repressing a promoter. In some embodiments, gene activityis regulated at the post-transcriptional level, for example throughregulation of RNA stability. In some embodiments, gene activity isregulated at the translational level, for example through regulation ofinitiation of translation. In some embodiments, gene activity isregulated at the post-translational level, for example throughregulation of polypeptide stability, post-translational modifications tothe polypeptide, or binding of an inhibitor to the polypeptide.

In some embodiments, gene activity is increased. In some embodiments,activity of at least one of a bacteriocin, immunity modulator,industrially useful molecule, poison molecule, or antidote molecule isincreased. Conceptually, gene activity can be increased by directlyactivating gene activity, or by decreasing the activity of an inhibitorof gene activity. In some embodiments, gene activity is activated by atleast one of: inducing promoter activity, inhibiting a transcriptionalrepressor, increasing RNA stability, inhibiting a post-transcriptionalinhibitor (for example, inhibiting a ribozyme or antisenseoligonucleotide), inducing translation (for example, via a regulatabletRNA), making a desired post-translational modification, or inhibiting apost-translational inhibitor (for example a protease directed to apolypeptide encoded by the gene). In some embodiments, a compoundpresent in a desired environment induces a promoter. For example, thepresence of iron in culture medium can induce transcription by aniron-sensitive promoter as described herein. In some embodiments, acompound present in a desired culture medium inhibits a transcriptionalrepressor. For example, the presence of tetracycline in an environmentcan inhibit the tet repressor, and thus allow activity from the tetOpromoter. In some embodiments, a compound found only outside of adesired culture medium induces transcription.

In some embodiments, gene activity is decreased. Conceptually, geneactivity can be decreased by directly inhibiting gene activity, or bydecreasing the activity of an activator of gene activity. In someembodiments, gene activity is reduced, but some level of activityremains. In some embodiments, gene activity is fully inhibited. In someembodiments, gene activity is decreased by at least one of inhibitingpromoter activity, activating a transcriptional repressor, decreasingRNA stability, activating a post-transcriptional inhibitor (for example,expressing a ribozyme or antisense oligonucleotide), inhibitingtranslation (for example, via a regulatable tRNA), failing to make arequired post-translational modification, inactivating a polypeptide(for example by binding an inhibitor or via a polypeptide-specificprotease), or failing to properly localize a polypeptide (e.g. failingto secrete a bacteriocin). In some embodiments, gene activity isdecreased by removing a gene from a desired location, for example byexcising a gene using a FLP-FRT or cre-lox cassette, or through loss ordegradation of a plasmid. In some embodiments, a gene product (e.g. apolypeptide) or a product produced by a gene product (e.g. the productof an enzymatic reaction) inhibits further gene activity (e.g. anegative feedback loop).

Genetic Modification of Microbial Organisms

Techniques of genetically modifying microorganisms are well known in theart. In some embodiments, a microorganism is genetically modified tocomprise nucleic acid sequence regulating the expression of, andencoding, at least one of bacteriocins, immunity modulators,industrially useful molecules, poison molecules, or antidote molecules.Polynucleotides can be delivered to microorganisms, and can be stablyintegrated into the chromosomes of these microorganisms, or can existfree of the genome, for example in a plasmid, extrachromosomal array,episome, minichromosome, or the like.

Exemplary vectors for genetic modification of microbial cells include,but are not limited to, plasmids, viruses (including bacteriophage), andtransposable elements. Additionally, it will be appreciated that entiremicrobial genomes comprising desired sequences can be synthesized andassembled in a cell (see, e.g. Gibson et al. (2010), Science 329:52-56). As such, in some embodiments, a microbial genome (or portionthereof) is synthesized with desired features such as bacteriocinpolynucleotide(s), and introduced into a microbial cell.

It can be useful to flexibly genetically modify a microbial cell, forexample to engineer or reengineer a microbial cell to have a desiredtype and/or spectrum of bacteriocin or immunity modulator activity. Insome embodiments, a cassette for inserting one or more desiredbacteriocin and/or immunity modulator polynucleotides into apolynucleotide sequence is provided. Exemplary cassettes include, butare not limited to, a Cre/lox cassette or FLP/FRT cassette. In someembodiments, the cassette is positioned on a plasmid, so that a plasmidwith the desired bacteriocin and/or immunity modulator combination canreadily be introduced to the microbial cell. In some embodiments, thecassette is positioned in the genome of the microbial cell, so that acassette with the desired bacteriocin and/or immunity modulatorcombination can be introduced to the desired location.

In some embodiments, plasmid conjugation can be used to introduce adesired plasmid from a “donor” microbial cell to a recipient microbialcell. Goñi-Moreno, et al. (2013) Multicellular Computing UsingConjugation for Wiring. PLoS ONE 8(6): e65986, hereby incorporated byreference in its entirety. In some embodiments, plasmid conjugation cangenetically modify a recipient microbial cell by introducing aconjugation plasmid from a donor microbial cell to a recipient microbialcell. Without being limited by any particular theory, conjugationplasmids that comprise the same or functionally same set of replicationgenes typically cannot coexist in the same microbial cell. As such, insome embodiments, plasmid conjugation “reprograms” a recipient microbialcell by introducing a new conjugation plasmid to supplant anotherconjugation plasmid that was present in the recipient cell. In someembodiments, plasmid conjugation is used to engineer (or reengineer) amicrobial cell with a particular combination of one or more bacteriocinsand/or immunity modulators. According to some embodiments, a variety ofconjugation plasmids comprising different combinations of bacteriocinsand/or immunity modulators is provided. The plasmids can compriseadditional genetic elements as described herein, for example promoters,translational initiation sites, and the like. In some embodiments thevariety of conjugation plasmids is provided in a collection of donorcells, so that a donor cell comprising the desired plasmid can beselected for plasmid conjugation. In some embodiments, a particularcombination of bacteriocins and/or immunity modulators is selected, andan appropriate donor cell is conjugated with a microbial cell ofinterest to introduce a conjugation plasmid comprising that combinationinto a recipient cell. In some embodiments, the recipient cell is a“newly engineered” cell, for example to be introduced into or forinitiating a culture. In some embodiments, the recipient cell is a“reengineered cell,” for example to introduce a new bacteriocin (andoptionally immunity modulator) activity to an existing culture that hasencountered a new type of invader cell, and/or to remove a bacteriocinactivity that is no longer desired in the culture.

Culture Media

Microbial culture environments can comprise a wide variety of culturemedia, for example feedstocks. The selection of a particular culturemedium can depend upon the desired application. Conditions of a culturemedium include not only chemical composition, but also temperature,amounts of light, pH, CO₂ levels, and the like.

In some embodiments, a genetically engineered microorganism as describedherein is added to a culture medium that comprises other microorganismsand at least one feedstock. In some embodiments, the culture mediumcomprises a compound that induces the activity or expression of abacteriocin and/or immunity modulator. In some embodiments, the culturemedium comprises a compound that represses the activity or expression ofa bacteriocin and/or immunity modulator. In some embodiments, a compoundthat induces the activity of the bacteriocin is present outside of thefeedstock, but not in the feedstock. In some embodiments, a compoundthat represses the activity of the immunity modulator is present outsidethe feedstock, but not in the feedstock.

The term “feedstock” is used herein in a broad sense to encompassmaterial that can be consumed, fermented, purified, modified, orotherwise processed by microbial organisms, for example in the contextof industrial processes. As such, “feedstock” is not limited to food orfood products. As used herein a “feedstock” is a category of culturemedium. Accordingly, as used herein “culture medium” includes, but it isnot limited to feedstock. As such, whenever a “culture medium” isreferred to herein, feedstocks are also expressly contemplated.

Genetically Engineered Microbial Cells

In some embodiments, genetically modified microbial cells are provided.Genetically modified microbial cells can be configured for a widevariety of purposes. In some embodiments, microbial cells comprisegenetic modifications to regulate the expression of at least one ofbacteriocins, immunity modulators, industrially useful molecules, poisonmolecules, or antidote molecules. In some embodiments, microbial cellscomprise genetic modifications to regulate the expression ofbacteriocins. In some embodiments, microbial cells comprise geneticmodifications to regulate the expression of immunity modulators.

In some embodiments, the genetically modified microbial cells aremodified to produce a product. In some embodiments, the product is agene product, for example a polypeptide or RNA. As such, polynucleotide“coding” sequence as referred to herein can refer to sequence encodingeither a polypeptide or an RNA. In some embodiments, microbial cells canbe configured to produce one or more gene products that contribute tosynthesis of a desired product, for example a carbohydrate, biofuel,lipid, small molecule, or metal. In some embodiments, the product issynthesized via the activity of one or more gene products of themicrobial cell. Optionally, synthesis of the product can also involvethe activity of one or more gene products of one or more other microbialcells. In some embodiments, microbial cells can be configured todecontaminate or decompose one or more substances in a culture media,for example a feedstock. The decontamination can be mediated wholly, orpartially by one or more gene products of the microbial cells. In someembodiments, microbial cells can be configured to scavenge for amaterial, for example a metal such as iron or a rare earth metal.

Controlling the Growth of Microbial Cells

In some embodiments, genetically modified microbial cells are modifiedto regulate the growth of other microbial cells. In some embodiments,the microbial cells regulate the growth of other microbial cells of thesame species or strain, for example their own clones. In someembodiments, the microbial cells regulated the growth of microbial cellsof a different species or strain, for example invaders. In someembodiments, a microbial cell secretes a bacteriocin to regulate othermicrobial cells. The regulation of each of the other microbial cells candepend on its expression (or lack thereof) of an immunity modulatorhaving protective effects against the particular the secretedbacteriocin.

As used herein “desired cell” and the like refer to a microbial cellwith at least one characteristic for which survival, growth, and/orproliferation of the microbial cell is desired, or at least an absenceof negative control of the cell's growth is desired. In someembodiments, a desired cell is in an appropriate environment, forexample its industrially-applicable feedstock. In some embodiments, adesired cell is a cell that is positively selected for, for example acell that has undergone a particular recombination even, or isexpressing high levels of a useful gene product. In some embodiments, adesired cell is a cell configured to neutralize contaminating cells, forexample pathogenic cells. In some embodiments a desired cell ispositively selected for by its expression of an immunity modulatorcorresponding to at least one bacteriocin that can be present in theenvironment. Without being bound by any particular theory, it iscontemplated that a microbial cell capable of neutralizing othermicrobial cells which lack a similar neutralizing function will have acompetitive advantage. As such, in some embodiments, a desired cell isselected for through its ability to neutralize other cells. In someembodiments a desired cell is positively selected for by expressing botha bacteriocin and a corresponding immunity modulator.

As used herein “undesired cell” and the like refer to a microbial cellwith at least one characteristic making survival, growth, orproliferation undesirable. In some embodiments, the undesired cell is aninvading microbial cell, for example a contaminating cell that hasentered a culture environment. In some embodiments, an undesired cellhas escaped from an appropriate culture medium, for example itsindustrially-applicable feedstock. In some embodiments, an undesiredcell has lost a particular plasmid, or has failed to undergo aparticular recombination event. In some embodiments, an undesired cellhas failed to produce, or produces low levels of desired gene product.In some embodiments, an undesired cell is selected against. In someembodiments, an undesired cell is selected against through by reducingthe cell's expression or activity of an immunity modulator that protectsagainst a bacteriocin in the environment. In some embodiments, anundesired cell is selected against through by reducing the cell'sexpression or activity of an immunity modulator that protects against abacteriocin secreted by the cell and clones thereof. In someembodiments, an undesired cell is selected against by reducing thecell's expression of a bacteriocin, thereby putting the cell at acompetitive disadvantage against other microbial cells.

FIG. 1 is a flow diagram depicting options for configuring a microbialcell to control the growth of a second microbial cell according to someembodiments herein. In some embodiments, a first microbial cell isprovided. In some embodiments, the first microbial cell secretes anactive bacteriocin 100. In some embodiments, the first microbial cell isnot desired 102. For example, in some embodiments, one or more of thefirst microbial cell being outside its industrial environment, a desiredenvironmental conditional for the first microbial cell being absent, thefirst microbial cell having made sufficient product, or the firstmicrobial cell lacking a recombination event or vector can make thefirst microbial cell undesirable in a particular environment at aparticular time 112. As such, when the first microbial cell is notdesired, its immunity modulator (corresponding to the bacteriocin) canbe inactive 122. For example, one or more of an immunity modulatorpromoter can be inactive, an immunity modulator transcriptionalrepressor can be active, post-transcriptional silencing (e.g. by aribozyme or antisense) can occur, a regulatable tRNA can not be induced,post-transcriptional silencing can occur (e.g. by a site-specificprotease, or a silencing post-translational modification), or a vectorencoding an immunity modulator can be absent 132. In some embodiments,when the first cell does not have an active immunity modulator, thefirst cell is neutralized by the bacteriocin 142 produced by other cellsin the culture. In some embodiments, a second microbial cell proceedswith growth 192 as a result of the first cell being neutralized.

In some embodiments, the first microbial cell is desired 106. Forexample, one or more of the first microbial cell being inside of itsindustrial environment, a desired environmental condition for the firstmicrobial cell being present, the first microbial cell having not yetmade sufficient product yet, or the first microbial cell havingundergone a recombination event or comprising a particular vector canmake the microbial cell desirable in a particular environment at aparticular time 116. As such, when the first microbial cell is desired,it can produce an active immunity modulator 126. For example, in someembodiments, the first microbial cell can be configured to have one ormore of a constitutive promoter for the immunity modulatorpolynucleotide, an activated (but not necessarily constitutive) promoterfor the immunity modulator polynucleotide, an inactive repressor ofimmunity modulator transcription, a regulatable tRNA that is induced tofacilitate production of the immunity modulator, an absence ofpost-translational and post-transcriptional silencing of the immunitymodulator, or a vector encoding the immunity modulator can be present136. As such, the first microbial cell can survive 146 in the presenceof bacteriocin secreted by the first microbial cell. As a result of thebacteriocin secreted by the first microbial cell, a second microbialcell can grow 192 or be neutralized 196, depending on whether the secondmicrobial cell has 172 or does not have 176 immunity modulator activity.

In some embodiments, the second microbial cell is desired 152. Forexample, one or more of a desired recombination event having occurred inthe second microbial cell, a desired vector present in the secondmicrobial cell, the second microbial cell producing a product of whichmore is desired (e.g. a positive feedback loop), or the immunity locusand the desired product being under the same transcriptional controlwhen appropriate levels of desired product are being transcribed can amake the second microbial cell desirable 162. When the second microbialcell is desired, it can provide immunity modulator activity to protectagainst the particular bacteriocin (or bacterocins) produced by thefirst microbial cell 172. For example, in some embodiments, the secondmicrobial cell can be configured such that an immunity modulatorpromoter is active (for example, a constitutive promoter), an immunitymodulator transcriptional repressor is inactive, there is a lack ofpost-transcriptional silencing, a regulatable tRNA being induced tofacilitate the expression of the immunity modulator, a lack ofpost-translational silencing (e.g. by a site-specific protease) of theimmunity modulator, or a vector encoding an immunity modulator can bepresent 182. As such, in some embodiments, when immunity modulatoractivity is provided, the second microbial cell can survive 192.

In some embodiments, a second microbial cell is not desired 156. Forexample, one or more of the second microbial cell being an invader (e.g.a contaminating cell), an undesired environmental condition for thesecond microbial cell (e.g. the presence of an undesired compound orcondition, or the absence of a desired compound or condition), thesecond microbial cell having produced product, but no more product beingdesired (e.g. a negative feedback loop), or an immunity modulator locusand desired product locus being under the same transcriptional controland transcript levels being undesirably low (e.g. indicating aninability to produce a desired product) can make the second microbialcell undesirable 166. As such, in some embodiments, there can be noimmunity modulator activity or an insufficient amount of an immunitymodulator to protect against the action of the bacteriocin in the secondmicrobial cell 176. For example, one or more of an immunity modulatorpromoter can be inactive, an immunity modulator transcriptionalrepressor can be active, post-transcriptional silencing of the immunitymodulator (e.g. by a ribozyme or antisense oligonucleotide) can occur, aregulatable tRNA can not be induced (so that expression of the immunitymodulator is not facilitated), post-transcriptional silencing of theimmunity modulator can occur (e.g. by a site-specific protease, or asilencing post-translational modification), or a vector encoding animmunity modulator can be absent 186. In some embodiments, the firstmicrobial cell provides secreted bacteriocin activity 100. As such, insome embodiments, the second microbial cell can be killed by thebacteriocin 196.

One skilled in the art will appreciate that, for this and otherfunctions, structures, and processes, disclosed herein, the functions,structures and steps may be implemented or performed in differing orderor sequence. Furthermore, the outlined functions and structures are onlyprovided as examples, and some of these functions and structures may beoptional, combined into fewer functions and structures, or expanded intoadditional functions and structures without detracting from the essenceof the disclosed embodiments.

For a large variety of genetically modified microbial cells, it can beuseful to control the growth of other microbial cells in the culture. Insome embodiments, a microbial cell controls the growth of othermicrobial cells in the culture. Exemplary functions and configurationsby which a first microbial cell can control the growth of one or moreother microbial cells according to some embodiments herein are describedin Table 4.

TABLE 4 Exemplary uses of bacteriocin systems in genetically modifiedmicrobial cells according to some embodiments herein Exemplaryconfigurations (according to some Exemplary Function embodiments)Biological containment: Immunity modulator activity only in the desiredculture medium, but not outside and bacteriocin activity at leastoutside of the desired culture medium; escape of the bacteriocinproducing cell outside the desired culture environment results incytotoxicity or growth inhibition of the bacteriocin producing cellGenetic guard Bacteriocin constitutively produced; genetic guardmicrobial organism does not produce gene products for modulatingindustrial process of interest; immunity modulator constitutivelyproduced (e.g under control of constitutive promoter) and/or geneticguard microbial organism is insensitive to the bacteriocin (e.g. a S.cerevisiae genetic guard producing bacteriocins that target E. coli)Selection of recombinants: Desired recombination event causes animmunity modulator to be restored in a bacteriocin-expressing host.Alternatively the immunity modulator can be restored only after thedesired recombination event. Vector stability: Immunity modulator (or atleast one gene essential for immunity is encoded on a plasmid, and acorresponding bacteriocin locus is encoded on chromosome); clones thatlose the desired plasmid lack immunity and are neutralized by thebacteriocin Minimization of genetic drift Immunity modulator activitydependent on production of industrial product (e.g. immunity modulatorexpression controlled by an operon, in which a repressor is active inthe absence of industrial product, and inactive in the presence ofindustrial product); if a mutation causes the microbial organism'sproduction of industrial product to fall below a desired level or cease,the microbial organism ceases to produce immunity modulator, and isneutralized by the bacteriocin. Selection for microbes presentingImmunity modulator is co-expressed with the gene of a high yield ofexpression interest; microbial organisms producing high levels ofexpression (and/or expressing gene product of interest can be selectedby increasing clones) bacteriocin concentration; microbial organismsproducing low levels of gene product of interest (e.g. having a low“industrial fitness”) are neutralized Destruction during fermentationDesired microbial cells constitutively express at least one ofcontaminating microbes. type of bacteriocin; secreted bacteriocinsneutralize invading microbial cells Desired microbial cells express atleast one type of bacteriocin when in the desired environment (e.g.bacteriocin is under the control of an inducible promoter that isactivated by an intermediate of the fermentation process); secretedbacteriocins neutralize contaminating cells Control of the ratio of aImmunity modulator activity is repressed by accumulated microbial flora.product made by a microbial cell; bacteriocins secreted by the microbialcell (or other cells) neutralize the microbial cell

FIG. 2 is a schematic diagram depicting a genetically engineeredmicrobial cell controlling the growth of at least one other microbialcell according to some embodiments herein. A first microbial cell 200can comprise a bacteriocin polynucleotide and a corresponding immunitymodulator polynucleotide. The bacteriocin polynucleotide can optionallybe integrated into the cell's genome, while the immunity modulatorpolynucleotide can optionally be integrated into a plasmid present inthe cell. In some embodiments an undesired clone of the cell 210 (a“non-expressing clone”) can lack immunity modulator activity, andoptionally can lack bacteriocin activity. The bacteriocin activity ofthe first microbial cell 200 can neutralize the non-expressing clone210. In some embodiments, an undesired clone of the cell 220 can lose aplasmid comprising the immunity modulator polynucleotide. Thebacteriocin activity of the first microbial cell 200 can neutralize theundesired clone 220. In some embodiments, the microbial cell 230 canescape from the desired environment, causing the clone to lack immunitymodulator activity. Bacteriocin activity from the escaped cell 230and/or clones of the escaped cell can neutralize the escaped cell 230.In some embodiments, the escaped cell 230 further comprises apoison-antidote system to facilitate killing of the escaped cell uponits escape.

FIG. 3 is a schematic diagram of a first genetically engineeredmicrobial cell 300 controlling the growth of a second geneticallyengineered microbial cell 310 and an invader cell 320 in a desiredenvironment according to some embodiments herein. The first geneticallyengineered microbial cell 300 can comprise a first bacteriocinpolynucleotide. The second genetically engineered microbial cell 310 cancomprise a second bacteriocin polynucleotide. Each of the first andsecond genetically engineered microbial cells (300 and 310) can comprisea first immunity modulator polynucleotide encoding resistance to thefirst bacteriocin, and a second immunity modulator polynucleotideencoding resistance to the second bacteriocin. If the second geneticallyengineered microbial cell 310 becomes undesired, it can lose firstimmunity modulator activity via any of the mechanisms discussed herein,and thus be controlled by the first bacteriocin activity from the firstgenetically engineered microbial cell 300. If an invader cell 320 entersthe desired environment, the first bacteriocin from the firstgenetically engineered microbial cell 300 and the second bacteriocinfrom the second genetically engineered microbial cell 310 can neutralizethe invader cell.

FIG. 4 is a schematic diagram of a first genetically engineeredmicrobial cell 400 controlling the growth of a first invader cell 410and a second invader cell 420 in a desired environment according to someembodiments herein. The first genetically engineered cell 400 cancomprise at least a first bacteriocin polynucleotide encoding a firstbacteriocin, and at least a second bacteriocin polynucleotide encoding asecond bacteriocin. The first genetically engineered cell 400 canproduce the first bacteriocin to neutralize a first invader cell 410.The first genetically engineered cell 410 can produce the secondbacteriocin to neutralize a second invader cell 420. In someembodiments, the first invader cell is of a different strain or speciesfrom the second invader cell. In some embodiments, the first invadercell responds to a different spectrum of bacteriocin activity than thesecond invader cell. In some embodiments, the first invader celltypically occupies a different ecological niche than the second invadercell.

FIG. 5 is a flow diagram illustrating methods of controlling the growthof at least a second microbial cell in culture according to someembodiments herein. The method can comprise culturing a first microbialcell in a culture medium comprising a second microbial cell underconditions in which the first microbial cell produces a bacteriocin at alevel sufficient to control the growth of the second microbial cell 510.The culturing of the first microbial cell can optionally be continuallymaintained for a period of time 520. In some embodiments, the culturingof the first microbial cell is maintained continually for at least 3days, for example at least 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15,16, 17, 18, 19, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85,90, 95, 100, 150, 200, 250, 300, 350, 400, 450, or 500 days, includingranges between any two of the listed values. A change in the culturemedium comprising a presence or increase in the levels or activity of athird microbial cell can be detected 530. The first microbial cell canbe re-engineered in response to the change to produce a secondbacteriocin at a level sufficient to control the growth of the thirdmicrobial cell 540. The re-engineered first microbial cell can becultured in the culture under conditions in which the first microbialcell produces a bacteriocin at a level sufficient to control the growthof the third microbial cell 550. The culture of the re-engineeredmicrobial cell can be repeated continually for a period of time 560. Insome embodiments, the culturing of the re-engineered microbial cell ismaintained continually for at least 3 days, for example at least 3, 4,5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 25, 30, 35,40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 150, 200, 250, 300,350, 400, 450, or 500 days, including ranges between any two of thelisted values.

In some embodiments, a first microbial cell can control the growth of asecond microbial cell. In some embodiments, a first microbial cell cancontrol the growth of a second microbial cell of the same strain as thefirst microbial cell. Each cell of the strain can comprise a bacteriocinpolynucleotide and an immunity modulator polynucleotide, such that theimmunity modulator, if expressed, protects against the bacteriocin. Assuch, if a clone of the strain loses expression of the immunitymodulator, it will be neutralized by bacteriocin activity from the samestrain. In some embodiments, the immunity modulator polynucleotide is incis to the bacteriocin polynucleotide. As such, even if the bacteriocinpolynucleotide and immunity modulator polynucleotide are both eliminated(e.g. if a plasmid is lost or a FLP-FRT cassette is excised),bacteriocin activity from other cells can still neutralize the cell. Insome embodiments, the immunity modulator polynucleotide is in trans tothe bacteriocin polynucleotide. The immunity modulator activity can belost when the microbial cell is undesired (for example, if a plasmid islost, or if a particular environmental condition induces a loss ofimmunity modulator activity). Accordingly, bacteriocin activity fromboth the microbial cell and also other cells of the strain can inducethe neutralizing of the microbial cell.

In some embodiments, a ratio of two or more microbial species or strainsis controlled. An exemplary control of ratios is illustrated in FIG. 3(see cells 300 and 310). In some embodiments, a first microbial strainor species loses an immunity modulator activity via any of themechanisms discussed herein when it is less desired than abacteriocin-producing second strain or species, increasing the ratio ofsecond strain or species to the first strain or species. In someembodiments in which the ratio of a first and second strain or speciesis controlled, a bacteriostatic bacteriocin or bacteriocins are selected(as opposed to bacteriocitic bacteriocins) so that the control of growthcan be readily reversible, and/or to minimize the risk of eliminatingeither of the strains or species. In some embodiments, a first microbialstrain or species produces a first bacteriocin under the control of apromoter that is activated in the presence of a compound or substance ofinterest, for example an intermediate or a product such as anindustrially useful molecule. As such, levels of the bacteriocinincrease as the levels of the compound of interest increase. In someembodiments, a second microbial strain or species produces (or catalyzesthe production of) the compound or substance of interest, but does nothave immunity modulator activity for the bacteriocin. As levels of thecompound or substance of interest increase, levels of the bacteriocinincrease, thus neutralizing the second strain (which lacks anappropriate immunity modulator or which has an insufficient amount of anappropriate immunity modulator to protect against the action of thebacteriocin). As such, relative levels of the first strain compared tothe second strain increase. In some embodiments, a first microbialstrain produces a first product and first bacteriocin activity, and asecond microbial strain produces a second product and second bacteriocinactivity. In some embodiments, the first product and the second productare intermediates in the same biosynthetic pathway. The first microbialstrain can provide a first and second immunity modulator activity, inwhich the second immunity modulator activity can protect against thesecond bacteriocin and is negatively regulated by accumulation of thefirst product (e.g. expression of the second immunity modulator isrepressed by the presence of the first product), and the first immunitymodulator activity can protect against the first bacteriocin. The secondmicrobial strain can also provide a first and second immunity modulatoractivity, except that the first immunity modulator activity isnegatively regulated by accumulation of the second product (e.g.expression of the first immunity modulator is repressed by the presenceof the second product). As such, when a relatively high amount of thefirst product has accumulated, the second immunity modulator in thefirst microbial strain is inactivated, and the microbial cells of thefirst strain are neutralized by the second bacteriocin, thus increasingthe ratio of the second strain to the first strain, and increasing therelative amount of second product to first product. When a relativelyhigh amount of the second product has accumulated, the first immunitymodulator in the second microbial strain is inactivated, and themicrobial cells of the second strain are neutralized by the firstbacteriocin, the increasing the ratio of the first strain to the secondstrain and increasing the relative amount of first product to secondproduct. As such, the ratio of the first stain to the second strain canbe adjusted, depending on relative levels of product. In someembodiments, an equilibrium of ratios of the first strain to the secondstrain is maintained. In some embodiments, an equilibrium of ratios ofthe first product to the second product is maintained. In someembodiments, the first microbial strain's second immunity modulatorresponds to a first environmental condition or compound, and the ratiobetween the first and second microbial strain is otherwise controlled asabove. In some embodiments, the second microbial strain's first immunitymodulator responds to a second environmental condition or compound, andthe ratio between the first and second microbial strain is otherwisecontrolled as above.

In some embodiments, it is desired that a microbial cell be containedwithin a particular environment, for example so that the first microbialcell can only survive in a particular culture medium such as industrialfeedstock. In some embodiments, a microbial cell comprises a bacteriocinpolynucleotide and an immunity modulator polynucleotide, such that theimmunity modulator corresponds to the bacteriocin. In some embodiments,when the microbial cell is in a desired environment, the microbial cellproduces an active bacteriocin and corresponding immunity modulator, butwhen the microbial cell escapes the desired environment, the microbialcell produces the active bacteriocin but no active immunity modulator.As a result, the microbial cell can grow in the desired environment, butis neutralized by its own bacteriocin when it escapes. For example, insome embodiments, the bacteriocin encoded by the bacteriocinpolynucleotide is constitutively expressed, while the immunity modulatoris expressed only when the microbial cell is in a desired environment.For example, in some embodiments, the bacteriocin encoded by thebacteriocin polynucleotide is constitutively expressed, while theimmunity modulator is expressed only when the microbial cell is in anenvironment. For example, in some embodiments, a transcriptionalactivator of the immunity modulator is only present in the desiredenvironment. For example, in some embodiments, the bacteriocin encodedby the bacteriocin polynucleotide and the immunity modulator isconstitutively expressed, but if the microbial cell escapes, theimmunity modulator is deleted (for example via the FLP-FRT system).Without being limited to any particular theory, if a genetic system forneutralizing an escaped microbial cell is not used within the cultureitself, there may be little or no selective pressure to maintain thesystem within the culture, so that mutations can accumulate which reduceor eliminate the functioning of that genetic system. As such, if themicrobial cell escapes from the culture, there is a possibility that thegenetic system will no longer function. In contrast, it is appreciatedherein that if a bacteriocin/immunity modulator system is useful bothwithin a culture (for example, to control the growth of othergenetically engineered cells in the culture, and/or to neutralizeinvading microbial cells), and also outside of a culture (for example,to neutralize a microbial cell that has escaped from culture), the usewithin the culture can provide selective pressure for the bacteriocinsystem to continue to function. Such selective pressure in accordancewith some embodiments herein can minimize genetic drift. Such selectivepressure in accordance with some embodiments herein can help to ensurethat if the microbial cell escapes from the desired culture environment,the bacteriocin/immunity modulator system will be functioning toappropriately neutralize the escaped cell. As such, in some embodimentsa single genetically engineered circuit, for example abacteriocin/immunity modulator system is useful both to neutralize othermicrobial cells within a desired culture environment, and further toneutralize a microbial cell and/or its clones upon escape from a desiredculture environment. It is contemplated in accordance with someembodiments herein, any or all of the configuration of bacteriocinsdisclosed herein can be tuned so that upon escape from the desiredculture environment, the escaping microbial organism will be neutralizedby its own bacteriocins (and/or bacteriocins of its direct or indirectprogeny, and/or bacteriocins of another escaped cell and/or its director indirect progeny).

In some embodiments, a microbial cell can control growth in two or moreways. In some embodiments, a microbial cell can perform two or more ofthe functions described in Table 4. In some embodiments, the microbialcell uses the same bacteriocin/immunity modulator pair for two or moredifferent functions. In some embodiments, the microbial cell uses afirst bacteriocin/immunity modulator pair for a first function, and asecond bacteriocin/immunity modulator pair for a second function. Forexample, in some embodiments, a microbial cell can express a bacteriocinwhich limits the growth of “non-expressing” clones that have lostimmunity modulator activity in a desired environment, and can alsoprovide containment within the desired environment by failing to expressits own immunity modulator (while still expressing bacteriocin) if themicrobial cell is outside of a desired environment. A schematicillustration of such two forms of growth regulation is illustrated inFIG. 2. For example, in some embodiments, a first microbial cell canexpress a bacteriocin which limits the growth of a second microbialcell, and can also neutralize the invading cell. A schematicillustration of such two forms of growth regulation is illustrated inFIG. 3. In some embodiments, two or more forms of growth control areprovided using the same bacteriocin-immunity modulator pair. In someembodiments, each form of growth control is provided using a differentbacteriocin immunity modulator pair. For example, a first immunity locuscan be present on a plasmid that also includes a polynucleotide encodinga desired product. A clone that loses the plasmid will be neutralized bya corresponding first bacteriocin. A second immunity modulatorpolynucleotide (corresponding to a second immunity modulator) can beintegrated into the genome of the microbial cell and can be silencedwhen the microbial cell escapes from its desired environment (forexample, the second immunity modulator polypeptide can be in a FLP-FRTcassette that is excised upon escape). As such, upon escape, themicrobial cell can be neutralized by the second bacteriocin.

It is noted that some embodiments described herein are compatible withpoison-antidote systems. As such, in some embodiments a microbial cell,in addition to a bacteriocin and immunity modulator further comprises apoison-antidote system configured to kill or arrest the cell when it isnot in a desired environment.

It can be useful to control the growth of two or more different types ofmicrobial cells. For example, an environment can comprise, or canpotentially comprise, two or more different types of undesired microbialorganisms. As different microbial organisms can have differentsusceptibility to bacteriocins (for example, by possessing differentprofiles of immunity modulators), a combination of two or morebacteriocins (e.g. a “cocktail” of bacteriocins) can be useful forcontrolling the growth of two or more microbial organisms. In someembodiments, a single microbial cell produces two or more differentbacteriocins for example, at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12,13, 14, 15, 16, 17, 18, 19, 20, 25, 30, 35, 40, 45, or 50 differentbacteriocins, including ranges between any two of the listed values. Insome embodiments, a mixture of two or more differentbacteriocin-producing microbial cells are provided, for example, 2, 3,4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 25, 30,35, 40, 45, or 50 different bacteriocin-producing microbial cells,including ranges between any two of the listed values. Optionally, oneor more of the bacteriocin-producing microbial cells can produce two ormore different bacteriocins.

It can be useful for a single microbial cell to regulate the growth oftwo or more different types of microbial cells. For example, it can bepossible for a first type of invading cell to possess immunity to afirst type of bacteriocin but not a second type of bacteriocin. As such,in some embodiments, a microbial cell comprises two or more bacteriocinpolynucleotides, each of which encodes a different bacteriocin (see,e.g. FIG. 4). In some embodiments, the microbial cell comprisespolynucleotides encoding at least three different bacteriocins, forexample at least three, four five, six, seven, eight, nine, ten, eleven,twelve, thirteen, fourteen, fifteen, sixteen, seventeen, eighteen,nineteen, twenty, or more different bacteriocins, including rangesbetween any two of the listed values. In some embodiments, two or morebacteriocin polynucleotides are under control of a single promoter. Insome embodiments, each bacteriocin polynucleotide under the control of asingle promoter comprises its own translational initiation site. In someembodiments, each bacteriocin polynucleotide is under the control of adifferent promoter. In some embodiments, two different bacteriocins areunder the control of two different but structurally or functionallyidentical promoters.

It can be useful for a microbial cell to control the growth of othermicrobial cells in its industrial environment, so as to help ensure theconsistent production of an industrial product, regardless of thegeographical location of the culture environment. Without being limitedby any particular theory, certain industrial products manufactured viamicrobial culture may have certain characteristics that result fromlocal microbial flora associated with a certain region (for example,Camembert cheese can have particular characteristics that result fromlocal microbial flora in Camembert, France, or sourdough bread can haveparticular characteristics that result from local microbial flora in SanFrancisco, Calif.). As such, it can be desirable to control themicrobial flora in a particular feedstock, so that a consistentindustrial product can be produced in a variety of geographicallocations. In some embodiments, a microbial cell is engineered toproduce bacteriocins to neutralize invading microbial cells found in avariety of geographical locations, which can ensure more consistentindustrial product characteristics for product produced in a variety oflocations. For example, a microbial cell designed to be used in aparticular industrial process and to be grown in a first geographiclocation may be engineered to express one or more bacteriocins effectiveagainst one or more invading organisms commonly encountered in the firstgeographic location. A microbial cell designed to be used in the sameindustrial process and to be grown in a second geographic location maybe engineered to express one or more bacteriocins effective against oneor more invading organisms commonly encountered in the second geographiclocation. Alternatively, a microbial cell designed to be used in aparticular industrial process and to be grown in two differentgeographical locations may be engineered to express on or morebacteriocins effective against one or more invading organisms commonlyencountered in each of the two geographical locations.

Frequently in industrial biotechnology, the goal is to work incontinuous process, and it is contemplated that the longer the processcontinues, the higher the probability of contamination. Accordingly, thecapacity to fight against contaminants can be useful for a continuousindustrial process. Synthetic microorganisms designed in laboratoriesare frequently used in industrial processes. As such, it can be usefulfor these lab-engineered “champions” to fight against undesired invadingmicrobial strains (for example wild-type strains from the environmentand/or cross-contaminants from another industrial process) and alsocontrol their potential genetic drift and escape in the environment. Inaccordance with some embodiments herein, invading microbial strains canbe fought, genetic drift can be minimized, and escape can be minimizedby inducing suicidal bacteriocins based genetic circuits.

It can be useful for a microbial culture to remain stable for acontinuous period of time, for example to ensure consistent industrialproduct characteristics over a continuous period of time. In someembodiments, a culture is stably maintained, at least in part, bybacteriocin-mediated neutralization of invading microbial cells. In someembodiments, a culture is stably maintained, at least in part, bybacteriocin-mediated control of ratios of two or more types ofgenetically engineered microbial cell in the culture. In someembodiments, a culture is stably maintained, at least in part, byreengineering a microbial cell already present in the culture. In someembodiments, the microbial cell is reengineered to add at least oneadditional bacteriocin activity (for example by adding a newbacteriocin, or expanding the expression of a bacteriocin alreadypresent) to neutralize a new type of invading microbial organism. Insome embodiments, the microbial cell is reengineered to remove at leastone bacteriocin activity that is no longer needed. Exemplary methods ofmaintaining a stable culture according to some embodiments herein areillustrated in FIG. 5. In some embodiments, a stable culture ismaintained for at least about 3 days, for example about 3, 4, 5, 6, 7,8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 25, 30, 35, 40, 45,50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 150, 200, 250, 300, 350,400, 450, or 500 days, including ranges between any two of the listedvalues.

Method for Detection of Ratios of Microbial Organisms

According to some embodiments herein, the ratios of two or moremicrobial strains or species can be controlled, depending on relativequantities of product, and/or compounds in the environment. Accordingly,in some embodiments, the ratios of the two or more microbial strains orspecies can be indicative of relative quantities of the product and/orcompounds in the environment. In some embodiments, relative quantitiesof microbes of a first strain or species and second strain or species asdescribed herein are detected, thereby indicating relative ratios orquantities of a first product or compound to a second product orcompound. Relative quantities of each microbial strain or species can bedetected in a variety of ways. In some embodiments, each strain orspecies comprises a unique oligonucleotide or polypeptide “bar code”sequence to facilitate specific detection. In some embodiments, eachstrain or species comprises a different bacteriocin (and thus adifferent bacteriocin polynucleotide), which can serve as a bar code. Insome embodiments, at least one of quantitative PCR, oligonucleotidearray analysis, flow cytometry, immunocytochemistry, in situhybridization, ELISA, immunoblotting, oligonucleotide spot blotting, orthe like is performed to determine relative quantities of the twodifferent microbial strains or species.

Method for Determining Modulation of Growth of Microbial Organisms inIndustrial Medium

In some embodiments, growth of microbial organisms in industrial mediumis modulated. Before adding a particular genetically engineeredmicrobial cell or combination of genetically engineered cells to anexisting industrial culture of microbial cells, it can be useful todetermine the effects, if any, of the bacteriocins on the growth of themicrobial cells in the existing industrial culture. In some embodiments,the effect of a particular bacteriocin or combination of bacteriocinsproduced by genetically engineered cells on microbial organisms isassessed. A medium or other composition comprising one or morebacteriocins produced by genetically engineered microbial cells asdescribed herein can be provided. In some embodiments, the mediumcomprises a supernatant comprising one or more bacteriocins. In someembodiments, the composition comprises one or more enriched or purifiedbacteriocins. In some embodiments, the supernatant or composition isthermally stable, for example to facilitate elimination of any microbestherein through high-temperature incubation, while retaining thefunction of any bacteriocins therein. In some embodiments, the medium orcomposition comprises a lyophilized material comprising bacteriocins. Insome embodiments, the medium or composition comprises a substrate boundto bacteriocins, for example a gel, a matrix, or beads. The medium orcompositions comprising bacteriocins can be added to the existingculture. In some embodiments, the medium or composition is added to aculture in an industrial culture environment. In some embodiments, themedium or composition is contacted with a sample of a culture from anindustrial culture environment. The growth or absence of growth ofmicrobial organisms in the industrial culture can be assessed forexample to determine whether the one or more bacteriocins are effectiveagainst a new invading organism which has appeared in the culture or todetermine the effects of the one or more bacteriocins on the existingorganisms in the culture.

Before a genetically engineered microbial cell is produced, it can beuseful to simulate the effects of one or more bacteriocins on aparticular culture environment. In some embodiments, a particularbacteriocin or combination of bacteriocins with desired activity in aknown culture environment is identified, and a microbial cell isconstructed to produce the desired bacteriocin combination ofbacteriocins. In some embodiments, a candidate bacteriocin orcombination of bacteriocins is contacted with a portion of an industrialculture of interest, and effects of the bacteriocin or bacteriocins onmicrobial organisms in the culture are identified. In some embodiments,a variety of bacteriocins is provided. In some embodiments, the varietyof bacteriocins is provided in a kit. In some embodiments, thebacteriocins were produced by microbial cells. In some embodiments, thebacteriocins are in supernatant from one or more microbial cells asdescribed herein. In some embodiments, the bacteriocins were chemicallysynthesized. One or more candidate bacteriocins or mixtures ofbacteriocins can be prepared, and can be contacted with a portion of theindustrial culture environment. In some embodiments, one or morebacteriocins are added to the supernatant of a bacteriocin-producinggenetically engineered cell that is already present in culture, forexample to ascertain the effects of engineering the cell to produce atleast one additional bacteriocin. In some embodiments, a sample from theindustrial culture environment is contacted with each candidatebacteriocin or mixture of bacteriocins. In some embodiments, eachcandidate bacteriocin or mixture of bacteriocins is added to the cultureenvironment. In some embodiments, effects of each candidate bacteriocinor mixture of bacteriocins are observed, for example as effects on thegrowth of at least one desired microbial cell in the culture, and/or thegrowth of at least one undesired microbial cell in the culture.

Upon identification of a desired combination of bacteriocins, amicrobial cell can be constructed to produce the desired combination ofbacteriocins. In some embodiments, an existing microbial cell, forexample a microbial cell that is producing a desired product orintermediate in industrial culture is reengineered to produce thedesired combination of bacteriocins. In some embodiments, the microbialcell is reengineered via plasmid conjugation. In some embodiments, a newcell is engineered to produce the desired combination of bacteriocinsand added to the industrial culture.

Genetic Guard Microbial Organisms and Systems

It can be useful for a bacteriocin-producing microbial organism toprotect other microbial organisms from undesired microbial organisms.Accordingly, in some embodiments, a “genetic guard microbial organism”is provided (which, as a shorthand, may also be referred to herein as a“genetic guard”). As used herein, a “genetic guard” refers to amicrobial organism or collection of microbial organisms that producesone or more bacteriocins so as to protect a “protected” microbialorganism that is immune to neutralizing effects of the bacteriocins, butdoes not itself produce the bacteriocins. The “protected” microbialorganism can perform a desired industrial process (for example,fermentation), while, as used herein, the “genetic guard” itself doesnot perform the desired industrial process. The genetic guard microbialorganism can express and secrete one or more bacteriocins. Optionally,the genetic guard microbial organism can constititvely express andsecrete one or more of the bacteriocins. The genetic guard microbialorganism can be non-susceptible to the bacteriocins produced by thegenetic guard, for example by producing immunity modulator(s) to thebacteriocin(s) secreted by the genetic guard, and/or by being a type ofmicrobial organism that is not susceptible to the to the bacteriocin(s)produced by the genetic guard (e.g. if the genetic guard comprises ayeast and secretes bacteriocins that specifically neutralize particularbacteria such as lactic acid bacteria). In some embodiments, theprotected microbial organism produces immunity modulator(s) to thebacteriocin(s) produced by the genetic guard. In some embodiments, theprotected microbial organism is not susceptible to the bacteriocinsproduced by the genetic guard (e.g. if the protected microbial organismcomprises a yeast, and the genetic guard microbial organism producesbacteriocins that specifically neutralize particular bacteria). In someembodiments, the protected microbial organism is not geneticallymodified (“non-GMO”). In some embodiments, the protected microbialorganism is non-GMO, but is from a strain selected to have desiredproperties, for example via selective pressure, and/or classicalmutagenesis. It is contemplated that even if the protected microbialorganism has desirable industrial properties, the protected microbialorganism may be insufficient at fighting-off one or more undesiredmicrobial organisms, for example invading local flora. Accordingly, insome embodiments herein, a genetic guard protects a protected microbialorganism from undesired microbial organisms. By way of example, non-GMOmicrobial organisms can be useful in a number of processes, for examplefood production, or purification such as water purification. In someembodiments, non-GMO “protected” microbial organisms are selected basedon their ability to destroy one or more contaminants (for example, knownwater contaminants), and a genetic guard is provided to protect theprotected microbial organisms from known or potential invading undesiredmicrobial organisms. In some embodiments, systems comprising a geneticguard as described herein are provided.

It can be useful to maintain a culture medium that does not containgenetically modified organisms, for example to perform particularindustrial processes, and/or to comply with certain production standardsor specifications. It is contemplated that in accordance with someembodiments herein, genetic guards can be separated from the “protected”microbial organism by a membrane that is permeable to bacteriocins, butnot to the genetic guard microbial organisms. As such, bacteriocinsproduced by the genetic guard can enter a culture medium occupied by theprotected microbial organisms, thus protecting the protected organismsfrom one or more undesired microbial organisms while the genetic guardremains separated from the microbial organism.

It is contemplated herein that a particular culture medium can beinvaded by and/or subject to a variety of undesired microbial organisms,which may susceptible to different bacteriocins or combinations ofbacteriocins. Accordingly, in some embodiments, the genetic guardmicrobial organism produces two or more different bacteriocins, forexample, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19,20, 2, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, or 100different bacteriocins, including ranges between any two of the listedvalues, for example 2 to 100, 2 to 50, 2 to 20, 2 to 10, 5 to 100, 5 to50, 5 to 20, 5 to 10, 10 to 100, 10 to 50, 10 to 20, 20 to 100, 20 to50, or 50 to 100 different bacteriocins. By way of example, in someembodiments, the genetic guard comprises a single E. coli strains, whichproduces 20 different bacteriocins. In some embodiments, the geneticguard produces a cocktail of bacteriocins. In some embodiments, thegenetic guard comprises a mixture of two or more differentbacteriocin-producing microbial organisms, for example, 2, 3, 4, 5, 6,7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 2, 30, 35, 40, 45,or 50 different bacteriocin-producing microbial organisms, so as toprovide a desired combination of bacteriocins. By way of example, insome embodiments, the genetic guard comprises a combination of 4different E. coli strains, each of which produces 5 differentbacteriocins (for a total of 20 different bacteriocins). In someembodiments, the genetic guard produces a cocktail of bacteriocins thattarget a particular category of microbial organism, for example lacticacid bacteria.

It can be useful for the genetic guard to be separated from a particularenvironment or culture medium, for example to maintain an industrialculture environment or feedstock free of genetically modified organisms(GMOs). In some embodiments, the genetic guard is physically separatedfrom the protected microbial organism. Optionally, the protectedmicrobial organism is non-GMO. In some embodiments, the genetic guard istemporally separated from the protected microbial organism. Optionally,the protected microbial organism is non-GMO. For example, temporalseparation in accordance with some embodiments can comprise adding thegenetic guard to a culture medium to neutralize invading organisms, andsubsequently adding the protected microbial organism to the culturemedium. Optionally, the genetic guard can be neutralized prior to addingthe protected microbial organism, for example via bacteriocins or apoison-antidote system as described herein. Optionally, the geneticguard can be neutralized by their own bacteriocins, for example byrepressing expression of the corresponding immunity modulator orimmunity modulators in the genetic guard. For example, temporalseparation in accordance with some embodiments can comprise culturingthe protected microbial organism in a culture medium, and subsequentlyadding the genetic guard to the culture medium.

In some embodiments, the genetic guard is positioned in a firstenvironment, and the protected microbial organism or organisms arepositioned in a second environment. The first environment can beseparated from a second environment by a membrane permeable tobacteriocins produced by the genetic guard but not the genetic guarditself. In some embodiments, the membrane is not permeable to theprotected microbial organism. In some embodiments, the first environmentis in fluid communication with the second environment. Without beinglimited by any theory it is contemplated that as bacteriocins typicallycomprise diffusible stable peptide molecules, the bacteriocins canreadily move in aqueous solution from the first environment to thesecond environment. In some embodiments, the first environment comprisesa first chamber, tank, or pond and the second environment comprises asecond chamber, tank, or pond. In some embodiments, the secondenvironment comprises an open-air environment. Optionally, an industrialprocess, for example fermentation, is taking place in the secondenvironment. In some embodiments, the first environment comprises acapsule positioned inside of the second environment. A variety ofmembranes are suitable for arrangements and systems in accordance withembodiments herein, so long as the membranes are permeable tobacteriocins, but not to genetic guards. In some embodiments, themembrane comprises at least one of a mesh, strainer, filter, selectivevalve, unidirectional valve, or porous membrane. In some embodiments,the membrane comprises one or more pores having a diameter smaller thanthe diameter of the genetic guard. In some embodiments, the bacteriocinsdiffuse through the membrane. In some embodiments, fluidic motion fromthe first environment to the second environment drives the movement ofthe bacteriocins. In some embodiments, the genetic guard is selectedbased on known or likely undesired microbial organisms in the culturemedium. In some embodiments, the genetic guard is changed after a periodof time. For example, in response to changes in the invading undesiredmicrobial organisms, the genetic guard can be adjusted so thatadditional bacteriocins are added, and/or some bacteriocins are removed.

In some embodiments, an existing microbially-mediated industrial processis performed in a new location, which is characterized by one or morepotential undesired microbial organisms. As the microbial organisms ofthe existing industrial process may not produce bacteriocins againstsome or all of the undesired microbial organisms of the new location, agenetic guard producing bacteriocins targeting the undesired microbialorganisms can be added to the culture medium in the new location. Assuch, the bacteriocins of the genetic guard can neutralize one or moreundesired microbial organisms, if present in the culture medium.

In some embodiments, the genetic guard produces a cocktail ofbacteriocins. The cocktail of bacteriocins can be collected while thegenetic guard is not, and the cocktail of bacteriocins can be contactedwith a culture medium of interest. As such, separation can be maintainedbetween the culture medium and the genetic guard. The skilled artisanwill appreciate that a number of methods are suitable for separating thebacteriocins from the genetic guard, so long as the methods do notsubstantially damage, denature, or destroy the bacteriocins. In someembodiments, the cocktail of bacteriocins is collected by filtering outthe genetic guard. In some embodiments, the cocktail of bacteriocins iscollected by centrifuging to separate the genetic guard from thebacteriocins. In some embodiments, the cocktail of bacteriocins iscollected by neutralizing the genetic guard. In some embodiments, thecocktail is stored prior to contact with the culture medium.

FIG. 6 is a schematic diagram illustrating a system 600 comprising agenetic guard in accordance with some embodiments herein. The system 600can comprise a first environment 610 and a second environment 620.Optionally, the second environment 620 can comprise an inlet 622 and/oran outlet 624. A fluid or culture medium to be treated, for examplepolluted water or feedstock can enter 626 via the inlet 622, and exit628 via the outlet. The first environment 610 can be separated from thesecond environment 620 by a membrane 630 that is permeable tobacteriocins, but is not permeable to genetic guard microbial organisms640. The first environment 610 can comprise genetic guard microbialorganisms 640, which produce bacteriocins that can move 650 between thefirst environment 610 and the second environment 620. The secondenvironment 620 can comprise protected microbial organisms 660, whichare not susceptible to the neutralizing effects of the bacteriocinsproduced by the genetic guard 640. Optionally, the protected microbialorganisms 660 can be non-GMO. However, if undesired microbial organisms670, 675 are present, the undesired microbial organisms 670, 675 can beneutralized by the bacteriocins. In some embodiments, the system 600comprises a treatment system for polluted water. In some embodiments,the system comprises a second inlet 623 so that fluid to be treatedenters 627 the first environment 610 before entering the secondenvironment 620. Optionally, the system can comprise the second inlet623 but not the first inlet 622. Optionally, the system can comprise thesecond inlet 623 and the first inlet 622. As such, the genetic guardmicrobial organisms 640 can secrete bacteriocins to neutralize invadingundesired organisms 670, 675, while maintaining physical separationbetween the genetic guard microbial organisms 640 and protectedmicrobial organisms 660.

FIG. 7 is a schematic diagram illustrating a genetic guard system 700that can be useful for photosynthetic production in accordance with someembodiments herein. The system 700 can comprise a first environment 710.Optionally, the first environment 710 can comprise an inlet 715. Thefirst environment 710 and optional inlet 715 can be in fluid and gascommunication with a second environment 720. The first environment 710can be separated from the second environment 720 by a membrane 730 thatis permeable to bacteriocins and gas, but is not permeable to geneticguard microbial organisms 640. The first environment 710 can comprisegenetic guard microbial organisms 640, which produce bacteriocins 740that can move between the first environment 710 and the secondenvironment 720. The second environment can comprise photosyntheticmicrobial organisms 750, for example photosynthetic microalgae.Optionally, the photosynthetic microbial organisms 750 are non-GMO. Asource of light 760 can be in optical communication with the secondenvironment 720. It is contemplated that the source of light 760 cancomprise sunlight and/or artificial light. CO₂ 770 can enter the secondenvironment 720, and can be used in combination with light from thelight source 760 for photosynthetic production by the photosyntheticmicrobial organisms 750. Optionally the CO₂ 770 can enter the inlet 715of the first environment 710, and enter the second environment 720through the membrane 730. Bacteriocins 740 produced by the genetic guardmicrobial organisms 740 can enter the second environment 720 through themembrane 730, and can neutralize undesired microbial organisms 780, 785in the second environment. Optionally, the second environment cancomprise an outlet 780, and biomass 790 produced by the photosyntheticmicrobial organism 760 can exit the second environment 720 via theoutlet 790. As such, the genetic guard microbial organisms 640 cansecrete bacteriocins to neutralize invading undesired organisms 670,675, while maintaining physical separation between the genetic guardmicrobial organisms 640 and photosynthetic microbial organisms 750 andbiomass 790.

Preservation and/or Storage of Feedstock

It can be useful to store a feedstock without performing an industrialprocess in the feedstock, for example to build up a reserve in caseadditional output is needed later on, to decrease output for the timebeing, and/or to transport the feedstock to a different location. Forexample, a feedstock for feeding animals can be harvested in the summer,and stored until winter, when it is used to feed animals. For example, afeedstock may undergo an initial round of fermentation to produce adesired component in the feedstock, or to destroy or remove a desiredcomponent in the feedstock, and/or to stabilize the feedstock forstorage, and the feedstock may then be preserved until it is to beconsumed.

It is contemplated herein that undesired microbial organisms cancontaminate a feedstock during storage, and/or consume or destroy one ormore components of the feedstock. For example, microbial organisms canbe selected or engineered to produce glucose from cellulose in afeedstock. However, in a feedstock comprising glucose, undesiredmicrobial organisms can catabolize the glucose. Accordingly, in someembodiments, a genetic guard is added to a feedstock so as to protectthe feedstock from one or more undesired microbial organisms duringstorage. In some embodiments, the feedstock undergoes an initial roundof processing (e.g. fermentation) to produce, remove, or destroy atleast one component (for example to stabilize the feedstock for storageand/or to provide a desired component in the feedstock such as glucosefrom cellulose), and the genetic guard then protects the feedstock fromsubsequent undesired microbial organisms. In some embodiments, thegenetic guard is physically separated from the feedstock by abacteriocin-permeable membrane during fermentation and/or duringstorage. It is contemplated that bacteriocin-mediated neutralization ofundesired microbial organisms in a feedstock in accordance with someembodiments herein can permit a feedstock to be stored stably for longperiods of time. In some embodiments, the feedstock is stably stored forat least one month, for example, at least one month, 2, 3, 4, 5, 6, 7,8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, or 24months.

In some embodiments, the genetic guard is contacted with the feedstock.In some embodiments, the genetic guard is already present in thefeedstock, and proliferation of the genetic guard is induced prior to orduring storage so that the genetic guard produces bacteriocins toneutralize undesired microbial organisms in the feedstock.

Methods of Preparing and Using Bacteriocin-Producing MicrobialOrganisms:

In accordance with some embodiments herein, bacteriocin-producingmicrobial organisms can be prepared for use in an industrial processwhich is subject to, or at risk of contamination or interference byundesired microbial organisms. In some embodiments, a circuit fordesired production of bacteriocins is designed, nucleic acid sequencesare engineered, and the circuit is assembled and introduced to a hostmicrobial organism.

FIG. 8 is a flow diagram illustrating methods of preparing and usingbacteriocin. The method can comprise identifying a set of genes codingfor bacteriocins targeting the undesired microbial organisms 810. Anapproach for identifying genes in accordance with some embodimentsherein comprises identifying bacteriocin genes using an electronicdatabase, for example bactibase, accessible on the world wide web atbactibase.pfba-lab-tun.org/main.php. The method can comprise designing aconstruct for expressing a bacteriocin, comprising integrating the geneset, promoter(s), and genetic regulatory elements 820. As such, aconstruct can be designed. Approaches for designing an appropriateconstruct in accordance with some embodiments herein can comprise usingparts databases, for example electronic databases such as the Biobricksfoundation parts database. It is contemplated herein that in accordancewith some embodiments, the skilled artisan can selected desiredcomponents (including, but not limited to bacteriocin nucleotides,promoters, and genetic regulatory elements) based on their identifiedfunctions, and engineer a construct with a desired functionality basedupon the identified functionality of these components. By way ofexample, functionalities of different possible components can be foundin one or more databases, such as the Biobricks catalog. A catalog ofBiobricks components is accessible on the world wide web atparts.igem.org. The method can comprise engineering the gene set withcompatible integration sites 830, which can allow the genes to beassembled in a desired manner and/or appropriately introduced to adesired host. A variety of suitable integration sites can be used, forexample restriction sites, substrates for an enzymatic recombinationreaction, or sequences for homologous recombination. In someembodiments, the gene set is synthesized. In some embodiments, a nucleicacid comprising the gene set is synthesized. In some embodiments, thegene set is provided in one or more vectors such as plasmids. The methodcan comprise assembling the circuits 840. The circuits can include oneor more bacteriocin nucleic acids, and a suitable promoter(s) andregulatory element(s). A variety of configurations of circuits can besuitable. In some embodiments, a single promoter drives expression ofmultiple bacteriocins and optional gene products of interest. In someembodiments, different bacteriocin nucleic acids are under the controlof different promoters. In some embodiments, a circuit is comprised in asingle construct such as a plasmid. In some embodiments, a circuit iscomprised in two or more constructs such as plasmids. In someembodiments, a nucleic acid comprising the complete circuit issynthesized. In some embodiments, the circuit is assembled usingconventional molecular cloning techniques, or a combination of nucleicacid synthesis and molecular cloning. Molecular cloning techniques arewell known to the skilled artisan. Many suitable molecular cloningtechniques are described in Green and Sambrook “Molecular Cloning: ALaboratory Manual” (2012) Cold Spring Harbor Laboratory Press; 4thedition, which is hereby incorporated by reference in its entirety. Themethod can comprise introducing the circuits into the desired host 850.Suitable hosts include, but are not limited to, naturally occurring,genetically engineered, and fully synthetic microbial organisms,including, but not limited to the exemplary microbial organismsdescribed herein. Optionally, the method includes performing phenotypiccharacterization 860, for example strain behavior. For example, it canbe useful to select for desired transformants or recombinants, confirmthat a strain is producing the desired bacteriocins, and/or confirm thata regulatory circuit is responsive to an appropriate stimulus such asindustrial precursor or product. The method can comprise industrialapplication comprising using the produced strain in the production plan870. For example, a bacteriocin-producing strain can be introduced to anexisting culture medium, or can be used as a starter culture for a newculture medium.

Kits

Kits are provided according to some embodiments herein. In someembodiments, the kits contain at least one of bacteriocins, bacteriocinpolynucleotides, immunity modulators, immunity modulatorpolynucleotides, other genetic elements (such as promoters, expressionvectors, conjugation plasmids, and the like), genetically engineeredmicrobial cells, and/or culture medium as described herein. In someembodiments, the kits further contain packaging, and/or instructions foruse of the contents therein. In some embodiments, the kits comprise avariety of bacteriocins, for example for use in ascertaining the effectsof a candidate bacteriocin or combination thereof on a cultureenvironment. In some embodiments, the kits comprise a variety ofbacteriocin polynucleotides and immunity modulator polynucleotides, forexample for constructing a microbial cell with desired characteristics.In some embodiments, the kits comprise a variety of donor microbialcells that comprise donor plasmids encoding a variety of combinations ofat least one bacteriocin and/or at least one immunity modulator.

Example 1 Protection of Cyanobacteria and Neutralization Upon Escape

A cyanobacterium comprising a biosynthetic pathway for a lipid isprovided. The cyanobacterium has been genetically engineered to comprisea bacteriocin polynucleotide under the control of a first promoter thatis constitutively active. The cyanobacterium comprises an immunitymodulator polynucleotide for an immunity modulator that protects againstthe bacteriocin, and that is under the control of a second promoter thatis only active in the presence of a precursor found in an industriallyuseful feedstock. The cyanobacterium is placed in the feedstock. Whileit is producing lipids in the feedstock, the cyanobacterium alsosecretes active bacteriocin, thus neutralizing invading microorganisms.Upon escape from the feedstock, the cyanobacterium no longer possessesimmunity modulator activity, but still produces bacteriocin, and thus isneutralized by the bacteriocin.

Example 2 Protection of Bacillus, Maintenance of a Plasmid, andNeutralization Upon Escape

A genetically engineered Bacillus cell is provided, comprising abacteriocin polynucleotide integrated into its chromosomal genome, and aplasmid comprising an immunity modulator polynucleotide for an immunitymodulator that protects against the bacteriocin as well as apolynucleotide encoding a polypeptide to be manufactured. Thebacteriocin is under the control of a constitutive promoter. Theimmunity modulator polynucleotide is under the control of a promoterthat is only active in the presence of a precursor found in theindustrially useful feedstock. As such, when the Bacillus is in thefeedstock, it produces the bacteriocin to kill invading microbial cells.Moreover, when Bacillus clones lose the plasmid, they become undesirable(as they no longer can produce the polypeptide to be manufactured), andas a result of also losing the immunity modulator, are killed by thebacteriocin. Upon escape from the feedstock, the Bacillus cell no longerpossesses immunity modulator activity, but still produces bacteriocin,and thus is neutralized by the bacteriocin produced by the othergenetically engineered Bacillus cells in its environment.

Example 3 Regulation of Levels of Two Partner Strains of S. cerevisiae

A first S. cerevisiae strain is provided. The first strain comprises abacteriocin polynucleotide under the control of a first promoter that isinduced by the presence of a metabolite. As such, the bacteriocin isexpressed more strongly as levels of the metabolite increase. Theencoded bacteriocin arrests the S. cerevisiae cell cycle, but isbacteriostatic, not bacteriolytic. The first strain also comprises animmunity modulator polynucleotide for conferring immunity to the firstbacteriocin under control of a promoter that is activated by a compoundpresent only in the industrial feedstock. A second, partner strain of S.cerevisiae comprises a polynucleotide encoding an enzyme that producesthe metabolite, but does not comprise a corresponding immunity modulatoractivity. As levels of the metabolite increase through activity of thesecond strain, the first strain produces more and more bacteriocin, thusarresting the cell cycle of the second strain, and reducing the relativeamount of cells of the second strain available. Meanwhile, the firststrain continues to proliferate. Accordingly, the relative ratio of thefirst strain to the second strain is increased, and buildup of themetabolite is reduced.

Example 4 Regulation of A. ferrooxidans by E. coli

An Acidithiobacillus ferrooxidans strain is engineered to produce storedenergy from the oxidation of Fe(II) to Fe(III) in a feedstock comprisingan iron source that diffuses Fe(II) into the feedstock. An E. colistrain is engineered to control the growth of the first strain of A.ferrooxidans. The A. ferroxidans strain comprises a nucleic acidencoding Colicin-Ia (SEQ ID NO: 56) under the control of a rus operonpromoter (SEQ ID NO: 549), and a nucleic acid encoding a Colicin-Iaimmunity modulator (SEQ ID NO: 464) under the control of a constitutivepromoter (B. subtilis ctc promoter, SEQ ID NO: 663). However, theferroxidans strain does not produce any Colicin-E1 immunity modulator.The E. coli strain comprises a nucleic acid encoding Colicin-E1 (SEQ IDNO: 54) and Colicin-E1 immunity modulator (SEQ ID NO: 465) under thecontrol of a constitutive promoter (SEQ ID NO: 651) integrated into itsgenome. However, the E. coli strain does not produce Colicin-Ia immunitymodulator (SEQ ID NO: 464). As the A. ferroxidans oxidizes Fe(II) toFe(III), levels of Fe(II) decrease. As such, activity of the ruspromoter decreases, and the A. ferroxidans produces lower levels ofColicin-Ia (SEQ ID NO: 54). Accordingly, any neutralization of the E.coli strain is minimized. The second strain of E. coli proliferates,producing higher levels of Colicin-E1 (SEQ ID NO: 54). The Colicin-E1neutralizes the A. ferroxidans, so that less A. ferroxidans is presentto oxidize Fe(II) into Fe(III). Accordingly levels of Fe(II) increaseagain. As Fe(II) accumulates, the A. ferroxidans produce higher levelsof Colicin-Ia (SEQ ID NO: 56), neutralizing organisms the second strainof E. coli. Accordingly, there in minimal E. coli producing Colicin-E1,and neutralization of A. ferroxidans is minimal as well. The A.ferroxidans proliferates, oxidizing the Fe(II) into Fe(III) and storingenergy.

Example 5 Genetic Guard for Ethanol Synthesis by Non-GMO MicrobialOrganism

A genetic guard in accordance with some embodiments herein is used toprotect a non-GMO microbial organism that produces ethanol from glucosein a feedstock. The genetic guard comprises an E. coli strain comprisingand expressing 20 different bacteriocin nucleic acids under the controlof a single constitutive promoter, and as such, produces 20 differentbacteriocins in approximately stoichiometric ratios. It is alsocontemplated that in accordance with some embodiments herein, anothersuitable option is to provide a genetic guard comprising five differentE. coli strains, each of which comprise and express five differentbacteriocins. The genetic guard is disposed in the first environment 610of a system as illustrated in FIG. 6. The bacteriocins diffuse through aporous membrane to enter the second environment. The porous membrane ismade of porous polytetrafluoroethylene that is permeable to bacteriocinsand liquid, but is not permeable to the genetic guard. Non-GMOfermenting S. cerevisiae are cultured in the second environment. Thenon-GMO fermenting S. cerevisiae produce ethanol from glucose in thefeedstock. The bacteriocins from the genetic guard neutralize invadingmicrobial organisms, preventing contamination of the feedstock andconsumption of the ethanol by invading microbial organisms. The porousmembrane maintains physical separation between thegenetically-engineered genetic guard and non-GMO fermenting yeast. Assuch, the fermenting yeast is protected from undesired microbialorganisms, while a portion of the feedstock is keep free of GMO's.

Example 6 Protection of Non-GMO Photosynthetic Microalgae by GeneticGuard

A genetic guard in accordance with some embodiments herein is used toprotect a non-GMO photosynthetic microalgae that produces biomass. Thebiomass can be suitable for a variety of downstream applications, forexample extracting compounds of interest, energy, or animal feed. Thegenetic guard comprises a mixture of 50 different B. subtilis strains,each of which produces a different bacteriocin. The genetic guard isdisposed in an aqueous first environment 710 of a system as illustratedin FIG. 7. The system further comprises an aqueous second environment720, which contains non-GMO photosynthetic microalgae, which yieldbiomass. The first environment is separated from the second environmentby a 0.5 μm fiberglass filter, so as to allow gas, liquid, andbacteriocins to pass between the first environment and secondenvironment, while blocking bacteriocins from passing between the firstenvironment and second environment. CO₂ enters the system through aninlet in the first environment, and diffuses through the firstenvironment and second environment. Sunlight enters the secondenvironment, and drives the photosynthetic microalgae to producebiomass. As a result, a high-glucose biomass is produced in the secondenvironment. The 50 different bacteriocins also diffuse from the firstenvironment to the second environment. The bacteriocins neutralizeinvading undesired microbial organisms, thus preventing contaminationthe biomass and preventing undesired microbial organisms frominterfering with biomass production and/or catabolizing the biomass.Biomass is harvested from the second environment via an outlet. As such,physical separation is maintained between genetically engineered geneticguard and non-GMO photosynthetic microalgae, while neutralizing invadingmicroorganisms in the second environment.

Example 7 Protection of Saccharomyces cerevisiae Against Lactic AcidBacteria Family (LAB)

A Saccharomyces cerevisiae is engineered to produce multiplebacteriocins active on Lactic Acid Bacteria (LAB). Leucococin C (SEQ IDNO: 368) and Diversin V41 (SEQ ID NO: 74) are shown to be active on LABbacteria according to the bactibase database, which is accessible on theworld wide web at bactibase.pfba-lab-tun.org/main.php. It is appreciatedthat as S. cerevisiae are not sensitive to Leucococin or Diversin V41,there is no need to integrate corresponding immunity loci into the S.cerevisiae. As such, Leucococin C (SEQ ID NO: 368) and Diversin V41 (SEQID NO: 74) are selected, and polynucleotides are encoding Leucococin C(SEQ ID NO: 369) and Diversin V41 (SEQ ID NO: 75) are provided. Thepolynucleotides encode Leucococin C (SEQ ID NO: 368) and Diversin V41(SEQ ID NO: 74), each fused to signal peptide from yeast mating factoralpha to facilitate secretion by the S. cerevisiae. The polynucleotidesare integrated into the genome of a single S. cerevisiae strain underthe control of a strong constitutive promoter, PPGK1(3-Phosphoglyceratekinase) (SEQ ID NO: 692). The transformation isperformed using standard homologous recombination. It is contemplatedherein that other suitable strong constitutive promoters include, butare not limited to PTEF1 (translation elongation factor) and PGAP(glycerinaldehyde-3-phosphate dehydrogenase) (a list of constitutiveyeast promoters is accessible on the world wide web atparts.igem.org/Promoters/Catalog/Yeast/Constitutive). The bacteriocinactivity expressed by the transformed S. cerevisiae is measured byinhibitory assays on LAB cultures invading the production plan. As themakeup of undesired microbial organisms invading the feedstock changesover time, S. cerevisiae strains producing additional, fewer, and/ordifferent bacteriocins can be produced and introduced into theindustrial feedstock.

What is claimed is:
 1. A system for controlling growth of microbialorganisms in a culture medium comprising a genetically engineeredmicrobial cell, said genetically engineered microbial cell comprising:i) a first nucleic acid sequence under the control of a first promoter,the first nucleic acid sequence encoding a secreted bacteriocin whichcontrols the growth of a second microbial cell, said secretedbacteriocin capable of inhibiting or preventing reproduction of saidgenetically engineered microbial cell in the absence of a cell immunitymodulator that confers resistance to said secreted bacteriocin; ii) afirst gene expression system genetically engineered to express thesecreted bacteriocin encoded by the first nucleic acid sequence; andiii) a second gene expression system comprising an expression vectorcomprising a second nucleic acid sequence which encodes the cellimmunity modulator that confers resistance to said secreted bacteriocin,wherein said first nucleic acid sequence is on a chromosome and whereinsaid expression vector comprising said second nucleic acid sequence is aplasmid; wherein said second gene expression system is geneticallyengineered and is capable of permitting transcription,post-transcriptional expression, and post-translational activity of saidcell immunity modulator, and is further capable of decreasing oreliminating at least one of: transcription of the second nucleic acidsequence which encodes the cell immunity modulator; post-transcriptionalexpression of the cell immunity modulator encoded by the second nucleicacid sequence; or post-translational activity of the cell immunitymodulator encoded by the second nucleic acid sequence, said second geneexpression system comprising at least one of: (a) a second promoteroperably linked to the second nucleic acid sequence which encodes thecell immunity modulator, the second promoter capable of being inactiveconcurrent with expression of the secreted bacteriocin by the first geneexpression system; (b) a second promoter operably linked to the secondnucleic acid sequence which encodes the cell immunity modulator, and anucleic acid encoding a transcriptional repressor configured to repressthe second promoter while the first gene expression system is active;(c) a ribozyme or antisense oligonucleotide complementary to at least aportion of the second nucleic acid sequence which encodes the cellimmunity modulator, the ribozyme or antisense oligonucleotidegenetically engineered to be expressed while the first gene expressionsystem is active; (d) a regulatable tRNA specific for a transcript ofthe second nucleic acid sequence which encodes the cell immunitymodulator, and genetically engineered to not be induced while the firstgene expression system is active, wherein when neutralizing an undesiredsecond microbial cell is desired, the first gene expression system isactive, and the second gene expression system permits transcription,post-transcriptional expression, and post-translational activity of saidcell immunity modulator, thereby allowing said secreted bacteriocin toinhibit or prevent the reproduction of the second microbial cell in theculture medium.
 2. The system of claim 1, wherein when at least one of(a) growth of the genetically engineered microbial cell is undesired,(b) a desired environmental condition is absent, or (c) a desired growthcondition is absent, the second gene expression system reduces oreliminates the transcription of the second nucleic acid sequence whichencodes the immunity modulator, post-transcriptional expression of thecell immunity modulator, or post-translational activity of the cellimmunity modulator, thereby permitting the secreted bacteriocin to killor arrest reproduction of the genetically engineered microbial cell. 3.The system of claim 1, wherein said genetically engineered microbialcell has been genetically engineered to make a desired product.
 4. Thesystem of claim 3, wherein said secreted bacteriocin further has beenselected to maintain at least one condition within a culture in whichsaid genetically engineered microbial cell is producing said desiredproduct.
 5. The system of claim 4, wherein the culture comprises atleast one invading microbial organism or at least one undesired cellthat is selected against by reducing or eliminating the undesired cell'sexpression or activity of the immunity modulator that protects againstthe secreted bacteriocin.
 6. The system of claim 4, wherein the at leastone condition within a culture comprises controlling the growth of thesecond microbial cell, wherein the second microbial cell is a commoncontaminate of the culture.
 7. The system of claim 1, wherein saidsecond microbial cell is a different strain, species or genus than saidgenetically engineered microbial cell.
 8. The system of claim 1, whereinsaid bacteriocin kills said second microbial cell.
 9. The system ofclaim 1, wherein said bacteriocin reduces the growth rate of said secondmicrobial cell.
 10. The system of claim 1, wherein said geneticallyengineered microbial cell is selected from the group consisting ofbacteria, yeast, and algae.
 11. A culture comprising the geneticallyengineered microbial cell of claim 1, wherein said culture furthercomprises the second microbial cell, wherein the presence of the secondmicrobial cell is undesired, wherein said first microbial cell secretesthe secreted bacteriocin, and wherein the second microbial cell does notproduce said immunity modulator that confers resistance to said secretedbacteriocin, so that said secreted bacteriocin thereby inhibits orprevents the reproduction of said second microbial cell.
 12. A method ofcontrolling the growth of a second microbial cell in a culture medium,the method comprising: culturing the genetically engineered microbialcell according to claim 1 in a culture medium comprising said secondmicrobial cell under conditions in which said first microbial cellproduces a bacteriocin at a level sufficient to inhibit or prevent thegrowth of said second microbial cell.
 13. The system of claim 1, whereinthe genetically engineered microbial cell comprises a bacterial cell oryeast cell.
 14. The system of claim 1, wherein the first promoter isconstitutive.
 15. The system of claim 1, wherein the first promoter isregulatable.
 16. The system of claim 1, wherein said second geneexpression system comprises (a) the second promoter operably linked tothe second nucleic acid sequence which encodes the cell immunitymodulator, the second promoter genetically engineered to be inactiveconcurrent with expression of the secreted bacteriocin by the first geneexpression system.
 17. The system of claim 1, wherein said second geneexpression system comprises (b) the second promoter operably linked tothe second nucleic acid sequence which encodes the cell immunitymodulator, and the nucleic acid encoding the transcriptional repressorconfigured to repress the second promoter while the first geneexpression system is active.